In mouse brain, neurotoxicity induces increase in neuronal cell calcium (Ca2+) levels, triggering calpain activation and calpain-mediated cleavage of p35 (Cdk5r1) to produce the cytosolic p25 fragment (Lee et al. 2000). Mouse Cdk5r1 shows 98% sequence identity to the human ortholog, and the calpain complex subunits are also highly conserved between the two species. Two calpain catalytic subunits expressed in neurons, Capn1 (mu-calpain) and Capn2 (M-calpain) are 89% and 94% identical, respectively, to human counterparts. The regulatory subunits Capns1 and Capns2 are 94% and 92% identical to human proteins, respectively.