The insulin-producing β-cell, tasked with mediating glucose homeostasis via glucose-stimulated insulin secretion (GSIS), is central to the etiology of type 1 (T1D, loss of pancreatic β-cells) or type 2 diabetes (T2D, reduced functional β-cell mass).1–4 β-cells are exquisitely tuned to the milieu of external stimuli to modulate insulin expression, production, maturation, and secretion. The gene discussed is INS; the disease is type 2 diabetes mellitus.