Calpains play a myriad of roles in calcium (Ca2+)‐regulated cellular functions.13, 14 Their enzymatic activity is under the regulation of Ca2+ and calpastatin (CAST) that activates and inhibits them, respectively.14, 15 The activation of calpains is controlled within smaller range, however, the stability of this regulating system tends to be impaired with increase in age resulting in an uncontrolled calpain activation,16, 17 implicating these enzymes in many disease conditions including neurodegenerative diseases like AD. This evidence concerns the gene CAST and neurodegenerative disease.