Otoferlin (OTOF)

Otoferlin is a large (~1,997 amino acids) single-pass transmembrane protein of the ferlin family that contains multiple Ca2+-binding C2 domains and a C-terminal membrane anchor; it functions as a key Ca2+ sensor for synaptic vesicle exocytosis at inner hair cell ribbon synapses, where several C2 domains (except C2A) bind Ca2+ and phospholipids to promote and regulate SNARE-mediated membrane fusion and vesicle replenishment; loss-of-function mutations in the OTOF gene cause DFNB9 auditory synaptopathy with severe-to-profound sensorineural deafness, making OTOF a validated therapeutic target for gene replacement approaches in the inner ear

Other names

OTOFFer1L2ferlin family memberDFNB9-related protein

For otoferlin itself: acts as a Ca2+ sensor through several C2 domains to regulate and stimulate SNARE-dependent membrane fusion/exocytosis in hair cells. For investigational gene therapies: gene replacement delivering functional OTOF to restore hair cell synaptic transmission.