Calpain-3

Calpain-3, also known as CANP3, is a muscle-specific calcium-dependent protease belonging to the calpain superfamily. In humans, it is encoded by the CAPN3 gene located on chromosome 15q15.

Calpain-3 is primarily expressed in skeletal muscle and plays a crucial role in muscle maintenance and repair. Unlike some other calpains, calpain-3 undergoes autocatalytic proteolysis, meaning it cleaves itself. This autocatalytic activity is essential for its proper function and regulation. The precise mechanisms and roles of calpain-3 remain under investigation, but it is thought to be involved in myofibril remodeling, protein turnover, and signal transduction within muscle cells.

Mutations in the CAPN3 gene are a major cause of limb-girdle muscular dystrophy type 2A (LGMD2A), also known as calpainopathy. LGMD2A is an autosomal recessive disorder characterized by progressive muscle weakness and atrophy, primarily affecting the proximal muscles of the limbs. The severity of the disease can vary depending on the specific mutation and its impact on calpain-3 function.

Research on calpain-3 includes investigations into its precise enzymatic activity, its regulatory mechanisms, and its interactions with other proteins within the muscle cell. Understanding the role of calpain-3 in muscle health and disease is critical for developing potential therapies for LGMD2A and other muscle disorders. Its unique autocatalytic processing and muscle-specific expression make it a compelling target for drug development strategies aimed at restoring muscle function.