CAPN3(Calpain-3) is a calcium-regulated non-lysosomal thiol-protease. It has a broad endopeptidase specificity. CAPN3 is activated by micromolar concentrations of calcium and inhibited by calpastatin. It interacts with TTN/titin. Isoform I is skeletal muscle specific. Defects in CAPN3 are the cause of limb-girdle muscular dystrophy type 2A (LGMD2A). LGMD2A is both autosomal dominantly and recessively transmitted. It is characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. CAPN3 belongs to the peptidase C2 family and contains 1 calpain catalytic domain and 4 EF-hand domains.