Intracellular Ca2+ leak via RyR2 channels induces glucose intolerance associated with pancreatic beta cell ER stress, mitochondrial dysfunction and decreased insulin secretion.1 Our finding reveals that the interaction between JPH3 and RyR2 in human and mouse pancreatic tissues, which implicates JPH3 as a new regulator of RyR2 function, and downregulation of JPH3 might directly lead to RyR2 Ca2+ leak and impair RyR2-Ca2+ signaling. This evidence concerns the gene INS and Glucose intolerance.