Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at 'His-409'. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53 (PubMed:23357851, PubMed:27657329). Broad endopeptidase activity. Activated by micromolar concentrations of calcium and inhibited by calpastatin. Homodimer; via EF-hand domain 4 (PubMed:24846670). Interacts with TTN/titin (PubMed:14583192). Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis (PubMed:20634290). Interacts with SIMC1 (PubMed:23707407). Interacts with UTP25; the interaction is required for CAPN3 translocation to the nucleolus (PubMed:23357851, PubMed:27657329). Isoform I is skeletal muscle specific. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the peptidase C2 family. Calpain-3 mutations in LGMD2A