INS and diabetes mellitus: In this review, we first describe the role of calcium signaling in pancreatic beta cell function and secondly highlight and summarize recent progress on the implications of impaired calcium signaling in defective insulin secretion in hPSC-derived β cells, and consequently, how targeting calcium signaling might be a new and interesting strategy to improve in vitro differentiation into functional hPSC-derived pancreatic beta cells for diabetes therapy.