It is puzzling that up-regulated Reg expression in the Gpx1-/-, Sod1-/-, and dKO islets was associated with decreased islet β-cell mass and insulin secretion [11], while down-regulated Reg expression in Gpx1-OE islets was accompanied with islet hyperplasia, hyperinsulinemia, and augmented glucose-stimulated insulin secretion [12,13]. The gene discussed is REG1A; the disease is hyperinsulinism.