Ferlin

Ferlin refers to a family of large cytosolic proteins that play key roles in calcium-dependent membrane trafficking and membrane repair. The name derives from the Caenorhabditis elegans protein FER-1, which is involved in membrane fusion events. In vertebrates, ferlin proteins function as Ca2+-sensitive mediators of vesicle fusion and plasma membrane resealing following injury, contributing to cellular membrane integrity and trafficking processes.

Ferlin proteins are characterized by multiple C2 domains, which mediate Ca2+-dependent phospholipid interactions, and a single C-terminal transmembrane domain that anchors the protein to membranes. The N-terminal region is variable among family members, reflecting diverse tissue distribution and specialized functions. The domain architecture supports roles in vesicle docking, fusion, and membrane repair across different cell types.

In humans, the ferlin family includes several members such as dysferlin (DYSF), myoferlin (MYOF), otoferlin (OTOF), and the FER1L proteins (FER1L2–FER1L6). These proteins share the characteristic ferlin architecture but differ in tissue expression and physiological roles. Dysferlin is highly expressed in skeletal muscle and is essential for muscle membrane repair; mutations cause limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Otoferlin is critical for synaptic vesicle exocytosis in auditory hair cells, with mutations causing congenital nonsyndromic deafness. Myoferlin participates in muscle development and repair, while other FER1L proteins have diverse roles in membrane trafficking and endosomal processes.

Clinical research continues to explore ferlin proteins as potential targets for therapies in muscular dystrophy, hearing loss, and related membrane fusion disorders. Ferlin biology remains a focus for understanding Ca2+-dependent membrane dynamics in multiple tissues.