The calpains are a family of calcium-dependent cysteine proteases, with calpain I (μ-calpain) requiring micromolar calcium and calpain II (m-calpain) requiring millimolar calcium. Calpain inhibitor XI is a cell-permeable dipeptidyl α-ketoamide that acts as a reversible, and active-site inhibitor of calpain I and II (Kis = 140 nM and 41 nM, respectively). It weakly inhibits cathepsin B (Ki = 6.9 μM). Calpain inhibitor XI has been shown to be neuroprotective following focal ischemia and to delay apoptosis in injured mouse spinal cord neurons.