Dysferlin (DYSF) (DYSF)

Dysferlin is a 237 kDa transmembrane protein encoded by the DYSF gene, primarily localized to the sarcolemma and cytoplasmic vesicles of skeletal and cardiac muscle cells (UniProt: P59537). It functions as a key mediator of calcium-dependent membrane repair, utilizing its multiple C2 domains to facilitate the fusion of repair vesicles with the plasma membrane upon injury (PubMed: 10330348). Deficiencies in dysferlin expression or function result in dysferlinopathies, a group of muscular dystrophies including Limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy, characterized by progressive muscle weakness and elevated creatine kinase levels (NCBI Gene: 1755). Because the DYSF coding sequence exceeds the packaging capacity of standard adeno-associated virus (AAV) vectors, therapeutic development has focused on innovative dual-vector strategies and minigene approaches to restore protein expression (PubMed: 30633895). Current clinical research aims to stabilize the sarcolemma and prevent the chronic inflammation and muscle fiber loss associated with these genetic defects. These therapies seek to provide a functional copy of the gene to muscle cells, thereby restoring the natural repair mechanism and slowing disease progression.

Other names

Fer-1-like protein 1Dystrophy-associated fer-1-like proteinFER1L1LGMD2BMYOT

Restoration of dysferlin protein levels through gene replacement therapy or stabilization of the sarcolemma to compensate for repair deficits.