Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves CTBP1. Broad endopeptidase specificity. Binds 4 Ca(2+) ions. Activated by micromolar concentrations of calcium and inhibited by calpastatin. Forms a heterodimer with a small (regulatory) subunit CAPNS1. Translocates to the plasma membrane upon Ca(2+) binding. Undergoes calcium-induced successive autoproteolytic cleavages that generate a membrane-bound 78 kDa active form and an intracellular 75 kDa active form. Calpastatin reduces with high efficiency the transition from 78 kDa to 75 kDa calpain forms (By similarity). Belongs to the peptidase C2 family.