This review bridges biophysical membrane dynamics with genetic pathology, positioning ciliary lipids not merely as structural components, but as active orchestrators of ciliary gatekeeping, cilia motility, and cilia signal transduction.
Abstract
The ciliary membrane is an active, highly specialized lipid landscape that dictates ciliary identity and function. Distinct from the surrounding plasma membrane, it exhibits a tailored lipid architecture—enriched in specific phosphoinositides, cholesterol, and sphingolipids—that shapes membrane curvature and establishes spatial platforms for signaling cascades. Emerging evidence indicates that disrupting the lipid microenvironment gives rise to a distinct spectrum of ciliopathies, driven by mislocalized signaling receptors, impaired intraflagellar transport (IFT), and disintegrated inner structures. This review bridges biophysical membrane dynamics with genetic pathology, positioning ciliary lipids not merely as structural components, but as active orchestrators of ciliary gatekeeping, cilia motility, and cilia signal transduction. By remapping the molecular mechanics of lipid dysregulation in diseases such as Bardet‐Biedl syndromes, we highlight how targeting the ciliary lipidome opens new therapeutic avenues for human ciliopathies.
Emerging evidence indicates that cell-type-specific and temporally dynamic ciliary signatures determine signalling competence and disease susceptibility, and defining these signatures and the mechanisms that regulate their plasticity could lead to new therapeutic opportunities for ciliopathies and other cilia-associate...
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Primary cilia are microtubule-based organelles protruding from the cell surface, which are conventionally understood as passive cellular antennae that detect extracellular stimuli. However, emerging evidence redefines these microtubule-based organelles as dynamic, bidirectional hubs that integrate environmental sensing...
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The mammalian plasma membrane is characterized by its pronounced lipid asymmetry, including the exceptional enrichment of sphingomyelin (SM) in the exoplasmic leaflet. How this asymmetry influences cholesterol distribution and membrane organization remains a central and unresolved question in cell biology. The lipid...
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