In neurodegenerative disease models, the loss of function mutation in Niemann-Pick type C1 (NPC1) changes the spatial distribution of IP3R1, potentiates GPCR-mediated Ca2+ signals, and promotes IP3R-mediated mitochondrial Ca2+ uptake causing cytotoxicity (Tiscione et al., 2021). Here, ITPR1 is linked to neurodegenerative disease.