A calpain inhibitor is a molecule that reduces the proteolytic activity of one or more members of the calpain family, particularly the calcium-activated cysteine proteases calpain-1 and calpain-2 ^[1]. Calpains cleave selected peptide bonds within cellular proteins, and their inhibition limits this processing rather than directly preventing protein synthesis ^[1][2]. Inhibitors include synthetic small molecules, peptide derivatives, and the endogenous regulatory protein calpastatin. Many small-molecule inhibitors interact with the catalytic cleft, where electrophilic groups can engage the active-site cysteine; individual compounds differ in reversibility and activity against other cysteine proteases ^[2]. Calpastatin uses a distinct recognition mechanism involving several contacts with calcium-activated calpain. Its inhibitory segment occupies the substrate-binding cleft while a loop passes around the catalytic cysteine, avoiding cleavage of the inhibitor itself ^[3][4]. Each of its four inhibitory repeats can engage a calpain molecule ^[4]. Inhibition therefore encompasses chemically diverse interactions that suppress substrate cleavage, with specificity varying among compounds and calpain isoforms ^[1][2].