Calpain-3 (CAPN3) (CAPN3)

Calpain-3 (CAPN3) is a muscle-specific, calcium-dependent cysteine protease that plays a vital role in the maintenance and remodeling of the skeletal muscle sarcomere (UniProt P20807). It is uniquely characterized by its ability to bind to the giant protein titin, which serves to stabilize the enzyme and regulate its proteolytic activity within the muscle fiber (PubMed: 16123113). Mutations in the CAPN3 gene lead to Limb-girdle muscular dystrophy type 2A (LGMD2A), also known as calpainopathy or LGMDR1, which is characterized by progressive proximal muscle wasting (NIH: Genetic and Rare Diseases Information Center). Because the disease results from a loss of functional protein, therapeutic strategies focus on gene replacement. Current clinical candidates, such as ATA-100 (formerly GNT0006), employ adeno-associated virus (AAV) vectors to deliver a functional copy of the CAPN3 gene directly to skeletal muscle (Atamyo Therapeutics, 2024). This gene delivery approach aims to restore endogenous Calpain-3 levels, thereby preserving muscle structure and improving motor function in affected patients (ClinicalTrials.gov: NCT05695638).

Other names

Calpain L3Muscle-specific calcium-activated neutral protease 3p94CANP3LGMD2ALGMDR1

Gene replacement therapy using an adeno-associated virus (AAV) vector to deliver a functional copy of the CAPN3 gene to skeletal muscle cells, restoring the production of the Calpain-3 protease.