DYSF encodes dysferlin, a large sarcolemmal protein functioning as a calcium ion sensor critical for skeletal and cardiac muscle membrane repair 1. The protein regulates vesicle fusion with the sarcolemma, enabling rapid resealing of mechanically disrupted membranes through calcium-dependent phospholipid binding and vesicle trafficking 2. Dysferlin also interacts with immunological pathways and regulates neurotransmitter secretion, with roles in macrophage and monocyte activation 2. Mutations in DYSF cause dysferlinopathies, a major subgroup of autosomal recessive limb-girdle muscular dystrophies accounting for up to 30% of progressive recessive muscular dystrophies in certain geographical regions 2. Clinical presentations are highly variable, including Miyoshi myopathy (posterior calf involvement), limb-girdle patterns, distal anterior tibial weakness, and axial myopathy 1. Comprehensive genetic analyses have identified over 200 DYSF variants globally, with hotspot mutations (c.2997G>T worldwide; c.1375dup in Chinese populations) and clustering in specific domains 3. Currently, no medical therapies are available 1, though emerging gene therapy approaches using optimized mRNA delivery systems show promise for restoring dysferlin to endogenous levels 4. Cardiac and respiratory involvement occurs across dysferlinopathy subtypes, necessitating systematic screening 5.