As Reg1cp is mainly expressed in islet, we further investigated the function of WT-and Mut-Reg1cp in glucose homeostasis and found that Mut-Reg1cp individuals had higher incidence of T2D compared with WT-Reg1cp subjects and mice with islet-specific Mut-Reg1cp knock-in aggravated the disruption of glucose homeostasis, whereas WT-Reg1cp seemed to have no influence on glucose homeostasis. Here, REG1CP is linked to type 2 diabetes mellitus.