Intracellular calcium ion is tightly regulated to maintain cellular function and cell survival. signals have been proposed to activate signal for hormone secretion. Calbindin-D9k (CaBP-9k) is responsible for regulation of the distribution of cytosolic free calcium ion. The previous study demonstrated that calcium binding protein CaBP-9k contribute to control signal-dependent NAD(P)H formation, respiration, and ATP changes in intact cells. Those regulation determine cell survival and secretory function. Furthermore, in the latest article demonstrated that CaBP-9k expression in insulin secreting and CaBP-9k depletion cause hypoinsulinemia. CaBP-9k KO mice accumulate only a few amounts of abdominal fat compare to wild-type mice result from hypoinsulinemia. Decreased insulin levels impede fat storage into the adipose tissues and other metabolic organs like liver and skeletal muscles. On the other hand, insulin resistance leads to an increase in the amount of fatty acids in the blood circulation due to the loss of insulin's ability to suppress lipolysis. Therefore, the phenotypes in aged CaBP-9k KO mice are related with decrease insulin secretion or production. 6 months old CaBP-9k KO mice showed decreased islet volume, increased cell death marker such as capase-3 and TUNEL staining resulting from endoplasmic reticulum stress which can lead pancreatic β cell death. Collectively, our findings indicate that CaBP-9k play a critical role for protection of pancreatic β cell survival from ER stress which contribute to glucose homeostasis accompanying lipid metabolism.