In this study, we clearly demonstrated that when binding of CaM to RyR2 was stabilized pharmacologically in TM-induced AD-type cells or genetically in neural cells from AppNL-G-F mice, most AD-related phenotypes (i.e. ER stress, neuronal cell loss, and cognitive dysfunction), except for Aβ accumulation were rescued. The gene discussed is RYR2; the disease is Alzheimer disease.