Increased ITPR expression was reported in muscles from patients with AD and AR RYR1 CM.49,55 Even though InsP3Rs are calcium channels, they cannot functionally replace the RyR1 because of their different biophysical properties, mode of activation (they are ligand-gated channels and are physiologically activated by the second messenger inositol 1,4,5-trisphosphate), the fact that they are not coupled to the voltage sensing dihydropyridine receptor and most likely not located in the junctional face membrane. Here, RYR1 is linked to Alzheimer disease.