Of interest, loss-of-function mutations in calpain-3 are known to cause limb girdle muscular dystrophy type 2a (LGMD2a; also called calpainopathy) [27], and transgenic reduction of calpain-3 in mice causes severe Ca2+ dysregulation [54]. Here, CAPN3 is linked to autosomal recessive limb-girdle muscular dystrophy type 2A.