Using pharmacological and genetic approaches, we systematically confirmed the role of CHEK2 function in insulin secretion of EndoC-βH1 cells, healthy and T2D human islets, cynomolgus macaque islets, as well as in chow-fed, high-fat-diet (HFD)-fed and genetically obese leptin-deficient Lepob/ob (ob/ob) mice. The gene discussed is INS; the disease is type 2 diabetes mellitus.