Insulin-secreting β cell loss or dysfunction is a feature of both type 1 and type 2 diabetes. Strategies to restore β cell mass are limited, as sources of healthy islets are scarce and mature β cells are not readily expanded in vitro. In this issue of the JCI, Ou et al. report that mature β cell expansion can be induced in situ through epigenetic editing of regulatory elements in pancreatic tissue. Specifically, hypomethylation at imprinting control region 2 (ICR2) in human islets promoted β cell expansion. Importantly, transplantation of these epigenetically edited islets into diabetic mice reduced blood glucose levels. Together, these results support further evaluation of this strategy for restoring β cell mass in patients with diabetes.