Ferlin Family

The Ferlin protein family consists of proteins containing C2 domains, which play a key role in vesicle fusion and membrane transport. Mammals have six Ferlin proteins (Fer1L1-6), namely Dysferlin (DYSF), Otoferlin (OTOF), Myoferlin (MYOF), Fer1L4 (Ferlin 4), Fer1L5 (Ferlin 5), and Fer1L6 (Ferlin 6). These are classified into two categories based on the presence or absence of the DysF and FerA domains: Class I (containing DysF and FerA) and Class II (lacking DysF and FerA).
Ferlin proteins participate in intracellular vesicle transport and membrane repair processes through interactions with cytoskeletal motor proteins, other vesicle-related transport proteins, and transmembrane receptors or channels. They regulate vesicle fusion under the control of calcium signaling, affecting neurotransmission and receptor recycling. These proteins are associated with various signaling pathways, including intracellular calcium regulation and vesicle dynamics. For example, Dysferlin is directly involved in calcium-activated membrane repair, while Otoferlin is crucial for calcium-activated release of neurotransmitter vesicles in auditory transmission. Dysfunction of Ferlin proteins can lead to diseases such as muscular dystrophy and hearing loss. For instance, defects in Dysferlin cause progressive muscular dystrophy, while defects in Otoferlin are associated with non-syndromic hearing loss^[1].