The proteolytic activity of μ- and m-calpains against diverse substrate proteins must be tightly controlled, as their abnormal activation has been implicated in the pathogenesis of many diseases such as Alzheimer's disease, muscular dysfunction, myocardial infarct, and tumor progression [26–31, 35, 47–49, 53, 55]. This evidence concerns the gene CAPN2 and early-onset autosomal dominant Alzheimer disease.