Structurally, the primary cilium is an elegant piece of cellular engineering. It is anchored by the mother centriole-derived basal body, which during the G0/G1 phase or differentiation docks at the plasma membrane and nucleates a 9+0 microtubule axoneme enclosed in a specialized ciliary membrane. Assembly, maintenance and signaling competence depend on intraflagellar transport, in which IFT-A and IFT-B complexes ride along the axoneme with kinesin-2 and cytoplasmic dynein-2 motors, ferrying cargo in both directions. At the ciliary base, transition fibers and the transition zone act as a selective gate, restricting which receptors, ion channels, transporters and signaling molecules can enter. This selective compartmentalization is what allows the cilium to function as a spatially restricted signaling hub rather than a simple membrane protrusion, concentrating machinery for Hedgehog, G protein-coupled receptor, calcium, receptor tyrosine kinase, TGF-beta and Wnt pathways within a nanometer-scale compartment.

The review’s central conceptual move is to treat the cilium as plastic rather than static. Environmental cues continuously remodel its assembly, length, composition and signaling output. Glucose deprivation, for example, promotes cilium formation in cultured cells mainly through inactivation of the nutrient sensor mTORC1 rather than through autophagy, and intriguingly it increases the proportion of ciliated cells while shortening the cilia themselves, showing that assembly and morphology are regulated separately. Glutamine deprivation tells an even more dramatic story in pancreatic ductal adenocarcinoma: the stress induces a protein called melanophilin, which accumulates at the basal body and drives ciliary regrowth, and the reassembled cilia amplify phospholipase C-gamma1 signaling in a feedforward circuit that promotes metastasis. Endogenous metabolic programs matter too. Local phosphoinositide remodeling at the centrosome recruits tau tubulin kinase 2, triggering removal of CP110, a cap that blocks axoneme extension, while cholesterol accessibility within the ciliary membrane modulates Smoothened activity in the Hedgehog pathway. Conversely, activation of SREBP1-driven lipogenesis and fatty acid synthesis suppresses ciliogenesis, in part by distorting vesicular trafficking.

Mechanical forces provide a second major class of inputs. In renal epithelial cells, urinary flow bends the apical cilium and activates calcium signaling through the polycystin-1 and polycystin-2 complex, proteins whose disruption causes polycystic kidney disease. Cilia-mediated flow sensing also regulates shear-dependent apical endocytosis in proximal tubules, linking mechanotransduction to reabsorptive function. In vascular endothelium the picture is context-dependent: cilia are retained under static or disturbed-flow conditions, whereas sustained laminar shear promotes ciliary shortening or disassembly, altering the cell’s capacity for cilia-dependent nitric oxide production. In bone, cilia deflect under dynamic fluid flow and are required for osteogenic responses and flow-induced calcium deposition in osteoblasts; in cartilage, they mediate compression-induced ATP release that regulates the extracellular matrix. Even substrate stiffness matters, since rigid matrices can suppress ciliogenesis through actomyosin tension-driven nuclear deformation and keratin-associated protein upregulation.

Oxygen tension adds a third layer of regulation. The von Hippel-Lindau protein, an E3 ubiquitin ligase that degrades HIF-alpha, localizes to the cilium and basal body, where it supports microtubule stability and cilium maintenance; loss of pVHL impairs ciliogenesis in renal-derived cells, and restoring it rescues cilium formation. Under hypoxia, HIF-2alpha can interact with the transport protein IFT88 to promote ciliogenesis and influence MEK/ERK signaling. The authors are careful to note that cilia are not universal hypoxia sensors but rather context-dependent platforms connecting oxygen-responsive signaling to localized ciliary regulation. Intracellular microRNAs form a distinct regulatory class: miR-129-3p promotes ciliogenesis by targeting CP110 and modulating actin dynamics, miR-669a-5p promotes ciliary elongation, and miR-182 and miR-183 are essential for maintaining the cone photoreceptor outer segments, which are highly specialized primary cilia required for vision.

Nowhere is the metabolic role of cilia more vivid than in the pancreatic islet. Beta-cell cilia compartmentalize receptors that regulate hormone secretion: insulin stimulation recruits insulin receptor isoform A to the cilium, and disrupting ciliary integrity attenuates downstream PI3K/Akt signaling. In Bbs4-deficient mice, ciliary dysfunction delays glucose clearance and impairs insulin secretion. Cilia-localized GPCRs add further control: free fatty acid receptor 4 and prostaglandin E2 receptor 4 enhance glucose-stimulated insulin secretion through cAMP-dependent pathways, while somatostatin receptor 3, activated by delta-cell somatostatin, lowers ciliary cAMP and triggers cilia-restricted calcium signaling that drives GLI2 nuclear translocation, tying GPCR signaling to the Hedgehog axis that maintains beta-cell identity. Recent work even identified endogenous GLP-1 receptors on beta-cell cilia, with loss of cilia blunting liraglutide-induced cAMP, calcium and insulin secretion. Endothelial cilia support the islet too, facilitating VEGFR2 internalization and downstream ERK and Akt signaling needed for vascularization and glucose delivery.

Lipid metabolism reveals the cilium’s capacity to integrate opposing signals. Cilium-dependent Hedgehog signaling suppresses the adipogenic transcriptional program, inhibiting fat cell differentiation, while lipid-raft organization at the ciliary base supports Akt-dependent adipogenesis and omega-3 fatty acid activation of ciliary FFAR4 initiates it. In muscle and brown fat, cilium-dependent Smoothened-calcium signaling activates AMPK, promoting glucose uptake and Warburg-like reprogramming. In renal epithelial cells, cilia couple extracellular cues to LKB1-AMPK signaling and mTORC1 suppression, and they sense fluid flow to promote lipophagy, mobilizing fatty acids from lipid droplets for mitochondrial beta-oxidation and ATP production. Prolonged shear stress promotes cilium-dependent mitochondrial biogenesis, increasing mitochondrial mass, DNA content, oxidative phosphorylation and ATP output through AMPK-PGC1alpha and TFEB-dependent programs, while decreased IFT88 expression with ciliary shortening is associated with impaired mitochondrial function in cisplatin-induced tubular injury.

Disease connections run deep. In the vasculature, endothelial cilia are enriched at arterial branch points where atherosclerosis preferentially develops, and loss of endothelial cilia promotes inflammatory activation and accelerates plaque progression; lipid droplet accumulation in endothelial cells sequesters palmitic acid, suppresses S-palmitoylation of ciliary proteins and impairs ciliogenesis. In reproduction, endometrial stromal cilia mediate Hedgehog-dependent epithelial-stromal communication during decidualization, and in endometriosis the cilia are shorter and decidualization responses reduced, with TGF-beta1 suppressing ciliogenesis by downregulating KIF3B. Trophoblast cilia are shortened in preeclamptic placentas, where inflammatory cytokines impair Hedgehog signaling and motility, and deleterious variants in the dynein-2 heavy chain gene DYNC2H1 have been identified in euploid recurrent pregnancy loss. In obesity, the melanocortin 4 receptor signals from hypothal neuronal cilia to suppress appetite, and MC4R-bearing cilia shorten with aging and overnutrition, reducing melanocortin sensitivity, energy expenditure and thermogenesis. Human type 2 diabetic islets show shortened beta-cell cilia and reduced beta-cell to delta-cell contacts, while classical ciliopathies such as Bardet-Biedl syndrome combine obesity with BBSome-dependent defects in mitochondrial dynamics.

Cancer adds a final, paradoxical dimension. Many tumors lose primary cilia as cells re-enter the cell cycle, yet under genotoxic or nutrient stress some cancer cells reassemble or elongate them as an adaptive survival strategy. Cisplatin-resistant pancreatic cancer cells regrow cilia through DNA damage signaling, and disrupting ciliogenesis resensitizes them; in glioblastoma, blocking ciliogenesis increases sensitivity to temozolomide and radiation. In neurodegeneration, LRRK2 mutations in Parkinson’s disease block ciliogenesis and cilia-dependent Sonic hedgehog signaling, while loss of cilia impairs clearance of damaged mitochondria in dopaminergic neurons; in Alzheimer’s models, neuronal cilia near amyloid plaques are shortened. The authors emphasize that ciliary remodeling is neither uniformly protective nor pathogenic, and that defining the cellular and environmental contexts in which it helps or harms will be essential. With live ciliary signaling reporters, tissue-specific manipulation models and spatial multi-omics now emerging, the field stands poised to move from describing these organelles to decoding, and perhaps therapeutically rewiring, the sensory-metabolic conversations they conduct.

Subject of Research: The role of primary cilia as sensory organelles and metabolic signaling hubs in physiology and disease

Article Title: Primary cilium as a sensory organelle and metabolic hub in health and diseases

Article References: Hou, H.-T., Chao, Y.-Y., Li, J.-N., Peng, I.-C., Lin, T.-C., Chiu, W.-T., Wang, C.-Y., & Tsai, S.-J. (2026). Primary cilium as a sensory organelle and metabolic hub in health and diseases. Journal of Biomedical Science, 33(1), Article 92. https://doi.org/10.1186/s12929-026-01291-6

Image Credits: AI Generated

DOI: 10.1186/s12929-026-01291-6

Keywords: primary cilium, ciliogenesis, metabolism, Hedgehog signaling, mTORC1, mechanotransduction, mitochondria, diabetes, obesity, ciliopathies, cancer, neurodegeneration

The acute crisis, physicians concluded, was an episode of acute kidney injury superimposed on advanced, previously unrecognized chronic kidney disease, precipitated by the dehydration of her gastrointestinal illness. She had never undergone renal ultrasound, biochemical kidney function testing, or assessment of her estimated glomerular filtration rate, because she had never before sought medical care for her underlying condition. The case, published as a case report in Clinical Case Reports, documents how a rare multisystem genetic disorder called Bardet–Biedl syndrome went entirely undiagnosed into adulthood, allowing progressive kidney damage to accumulate unchecked until a routine infection brought the hidden disease to the surface.

Bardet–Biedl syndrome is a rare autosomal recessive ciliopathy, meaning it arises from defects in the primary cilium, a tiny antenna-like organelle that projects from nearly every cell in the body and coordinates crucial developmental and signaling pathways. The syndrome is defined by a constellation of features: rod–cone dystrophy of the retina that typically begins as night blindness and progresses to blindness, central obesity, extra fingers or toes known as polydactyly, intellectual disability, hypogonadism or genitourinary anomalies, and kidney involvement. Because the condition shows variable penetrance, its presentation can differ dramatically even among siblings in the same family, complicating recognition. In European outbred populations, prevalence is estimated at roughly one in 125,000 to one in 160,000 people, but isolated communities with founder mutations can carry far heavier burdens, most famously the Faroe Islands, where a single BBS1 splice-site mutation produces a prevalence of one in 3,700.

The patient in Lahore carried nearly the full textbook picture. Blind since age 19 after night blindness first appeared at age 8, she had a body mass index of 29, primary amenorrhea, childhood intellectual disability, bilateral polydactyly of both hands and feet, widely spaced eyes, strabismus, and a history of cystostomy for urethral stricture. Two of her siblings were affected by a similar constellation of problems, and she was born to first-cousin parents, a consanguinity pattern that dramatically raises the probability of homozygosity for recessive disease alleles. Laboratory workup added further findings: severe macrocytic anemia with hemoglobin of 6.8 g/dL, elevated alkaline phosphatase at 480 U/L, and an HbA1c of 8.2 percent with random glucose of 250 mg/dL, indicating poorly controlled diabetes mellitus that had also escaped prior diagnosis.

Imaging sealed the clinical picture. Abdominal ultrasound showed coarse liver echotexture, mild splenomegaly, and kidneys with increased echogenicity and reduced corticomedullary differentiation, hallmarks of chronic parenchymal damage. Computed tomography of the kidneys, ureters, and bladder then demonstrated bilaterally small kidneys, the right measuring 83 by 27 millimeters and the left 83 by 33 millimeters, with lobulated, irregular cortices consistent with longstanding scarring. In a young adult, kidneys of this size and texture represent years of accumulated nephron loss. The combination of retinal dystrophy, kidney disease, polydactyly, obesity, intellectual disability, primary amenorrhea, and affected siblings pointed decisively toward a hereditary ciliopathy, and the principal differential, Alström syndrome, was excluded because it does not typically involve polydactyly or intellectual disability. A clinical diagnosis of Bardet–Biedl syndrome was made, though genetic confirmation was not pursued because of resource limitations.

At the molecular level, BBS is strikingly heterogeneous: at least 26 genes have been identified, most encoding proteins essential for ciliary assembly and intracellular trafficking. Disruption of ciliary signaling, including the non-canonical Wnt pathway, is implicated in the cystogenesis and progressive nephron loss that characterize BBS-related kidney disease. Genotype–phenotype studies suggest that patients with variants in chaperonin-like genes such as BBS6, BBS10, and BBS12 tend to develop more severe chronic kidney disease than those with BBS1 variants, a finding that could eventually guide how intensively clinicians surveil renal function once sequencing becomes accessible in settings like Pakistan. Diagnostic criteria originally proposed by Beales and colleagues require either four primary features or three primary features plus two secondary ones, and a recent European Reference Networks consensus has updated the framework to incorporate molecular diagnosis alongside clinical findings. This patient fulfilled the primary criteria of rod–cone dystrophy, postaxial polydactyly, obesity, intellectual disability, genitourinary anomalies, and renal dysfunction.

What makes the case exceptional is timing. The mean age of clinical BBS diagnosis is around nine years, yet this patient reached her third decade without a formal syndromic diagnosis of any kind. Renal involvement affects more than half of BBS patients and is the leading driver of premature mortality in the syndrome, ranging from structural anomalies such as fetal lobulation and increased parenchymal echogenicity to cystic dysplasia and progressive loss of glomerular filtration. In the largest reported cohort, kidney failure requiring renal replacement therapy occurred in roughly 6 percent of adult and 5 percent of pediatric patients, and affected children tend to follow one of two trajectories, either developing severe chronic kidney disease early or remaining comparatively spared through childhood. An early warning sign, reduced urinary concentrating capacity producing polyuria and polydipsia, reflects tubular dysfunction tied to disrupted ciliary signaling and can flag declining renal function years before crisis.

Treatment of the acute episode followed standard nephrology practice. The patient received three sessions of hemodialysis, broad-spectrum antibiotics, intravenous fluids, and antipyretics, and improved over subsequent days with a notable recovery of urine output before discharge with strict follow-up advice. Her echocardiogram was normal, reassuring given that cardiovascular abnormalities have been documented in a subset of BBS patients. Longer-term management of the syndrome demands a genuinely multidisciplinary approach spanning nephrology, ophthalmology, endocrinology, genetics, and cardiology, with regular blood pressure monitoring, annual ophthalmologic evaluation, and periodic assessment of renal and metabolic parameters. Should her kidneys progress to outright failure, renal transplantation remains viable with outcomes comparable to the general population, although coexisting obesity can complicate both pre-transplant workup and post-transplant metabolic management. No disease-modifying therapy yet exists for the renal or retinal manifestations, making surveillance the principal tool for delaying irreversible complications.

The Pakistani context adds a public-health dimension. Roughly half to two-thirds of marriages in the country are consanguineous, most commonly between first cousins, a pattern that should, in principle, elevate the prevalence of autosomal recessive disorders like BBS. Yet reported Pakistani cases remain scarce, a paradox the report’s authors attribute to underdiagnosis rather than genuinely low prevalence, driven by limited access to ophthalmologic, nephrologic, and genetic testing. A recent case series from Multan described four affected individuals from two sibling pairs, illustrating both marked intrafamilial variability and diagnostic delay, and the literature now includes scattered reports from Dera Ismail Khan, Peshawar, Karachi, and Islamabad. Most patients present in childhood or adolescence with retinal and developmental features and are diagnosed clinically rather than genetically, and the present case appears to be among the few from Pakistan in which unrecognized chronic kidney disease progressed to acute kidney injury in adulthood before the underlying syndrome was ever identified.

The broader lesson reaches beyond one hospital ward. Bardet–Biedl syndrome’s features can appear so scattered across specialties, an eye problem here, extra digits there, obesity and developmental delay elsewhere, that no single clinician assembles the full picture until something acute forces the issue. Greater awareness among pediatricians, ophthalmologists, and family physicians, combined with systematic renal surveillance of children showing the syndrome’s cardinal features, could allow earlier diagnosis and potentially forestall exactly the kind of delayed, dramatic presentation seen in Lahore. Genetic counseling remains central to comprehensive care, informing families about recurrence risk and the value of screening apparently healthy relatives for subclinical complications. For this 27-year-old woman, the gastroenteritis that nearly overwhelmed her kidneys also finally gave her disease a name, and with it, at last, the possibility of coordinated care.

Subject of Research: Bardet–Biedl syndrome presenting as acute kidney injury on undiagnosed chronic kidney disease in a young adult

Article Title: Bardet–Biedl Syndrome Presenting With Acute Kidney Injury Revealing Previously Undiagnosed Advanced Chronic Kidney Disease in a Young Adult: A Case Report

Article References: Abbas, A., Amjad, N., Mufti, A. F., Waqas, M., Iqbal, M., Ali, H., Habib, A., Samadi, Y., & Haider, M. U. (2026). Bardet–Biedl Syndrome Presenting With Acute Kidney Injury Revealing Previously Undiagnosed Advanced Chronic Kidney Disease in a Young Adult: A Case Report. Clinical Case Reports, 14(10), Article e73672. https://doi.org/10.1002/ccr3.73672

Image Credits: AI Generated

DOI: 10.1002/ccr3.73672

Keywords: Bardet-Biedl syndrome, ciliopathy, acute kidney injury, chronic kidney disease, polydactyly, rod-cone dystrophy, consanguinity, Pakistan, hemodialysis, genetic diagnosis, primary cilium, rare disease