Caveolins, cavins, and caveolae: Lessons from human mutations

Caveolae are specialized plasma membrane invaginations enriched in cholesterol and sphingolipids, playing vital roles in signal transduction, lipid regulation, membrane trafficking, and mechanoprotection. Their formation and function depend on two protein families: caveolins and cavins. Caveolins are integral membrane proteins that contribute to the membrane's curvature and serve as scaffolds for diverse signaling molecules. Cavins support caveolins at the cytoplasmic surface to stabilize caveolar architecture and regulate key processes, including insulin signaling, nitric oxide synthase activity, and lipid droplet formation. Mutations in caveolin or cavin genes can disrupt caveolae formation and function, often impairing cholesterol handling and perturbing key signaling pathways. This has been observed in a spectrum of pathologies such as muscular dystrophies, cardiomyopathies, lipodystrophies, and various cancers. Given the importance of caveolins and cavins in membrane organization, understanding how specific mutations alter caveolin and cavin function is critical for elucidating the molecular basis of various disorders and in the development of targeted therapies. This review explores how caveolin and cavin mutations affect caveolae morphology, function, and signaling, thereby impacting physiology.