The proteolytic activity of calpain complexes is inhibited by binding to calpastatin (CAST) (Takano et al. 1995). Based on detailed structural studies of recombinant rat proteins, CAST associates with calcium-bound calpain heterodimers and occupies both sides of the calpain active site cleft (Hanna et al. 2008). CAST levels are reduced in Alzheimer disease (Sato et al. 2011).