The sigma-1 receptor (Sig-1R), located in mitochondria-associated endoplasmic reticulum membrane (MAM), usually binds to binding immunoglobulin protein (BIP/GRP78) as an ER chaperone to ensure the function and stability of certain signaling molecules, regulating calcium homeostasis, improving MAM function, and preventing the occurrence of ERS [8,9]. Here, HSPA5 is linked to amelogenesis imperfecta type 1G.