We have demonstrated that CS mutation in the KCNJ8 genes encoding for the Kir6.1WT/VM is responsible for severe injuries in the skeletal muscle of a murine model of CS, reporting how GOF mutation caused atrophy, necrosis, and loss of muscle with fibrotic replacement, inflammatory cell infiltration, up-regulation of autophagy genes, and reduced muscle strength in the slow twitching muscle and impairment of glibenclamide response (Scala et al., 2020b). This evidence concerns the gene KCNJ8 and Cowden syndrome 1.