Calpains are a family of intracellular Ca2+ dependent cysteine proteases. They respond to Ca2+ signals by cleaving many specific proteins, thereby irreversibly modifying their function(s). They are implicated in a variety of Ca2+ regulated cellular processes as well as various pathological phenomena, such as ischemic injury, muscular dystrophy, diabetes, cataract, atherosclerosis, Alzheimer’s disease, and cancer. Calpains represent potential therapeutic targets for drug discovery. This 27-residue peptide is derived from subdomain 1B of the repetitive domains of calpain, named peptide B27-WT. It is a potent inhibitor of calpain.