Ciliary Membrane Lipid Homeostasis in Health and Disease

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.