Calpain-3 (CAPN3)

Calpain-3 (CAPN3) is a muscle-specific, calcium-dependent cysteine protease essential for normal skeletal muscle function. It is unique among calpains due to its rapid self-autolysis and presence of specific insertion sequences (NS, IS1, IS2). CAPN3 is predominantly localized in the sarcomere, the basic contractile unit of muscle fibers, and is tightly regulated both by its own inhibitory fragments and interactions with sarcomeric proteins. CAPN3 regulates cytoskeletal remodeling, proteolytic turnover of structural proteins, and protein sumoylation, affecting muscle repair and maintenance. Mutations in the CAPN3 gene cause limb-girdle muscular dystrophy type 2A (LGMD2A), characterized by progressive weakness and wasting of the shoulder and pelvic girdle muscles. Despite its clear genetic link to disease, the endogenous substrates and precise medicine-relevant pathways of CAPN3 remain incompletely characterized, and no drugs specifically target this protease to date.

Other names

Calpain-3CAPN3p94CANP3CANPL3NCL1nCL-1Calcium-activated neutral proteinase 3Calpain L3Calpain p94Muscle-specific calcium-activated neutral protease 3New calpain 1LGMD2LGMD2ALGMDD4LGMDR1