Calpastatin is a widely distributed endogenous inhibitor protein specifically acting on calpain (Ca2+-dependent cysteine endopeptidase). This 27-residue peptide encoded by Exon 1B, including a 12-residue middle conserved sequence, shows strong inhibition against calpain I (low Ca2+-requiring form), and calpain II (high Ca2+-requiring form), but not against papain or trypsin.