To date, important windows into disease mechanisms have been elucidated from either (1) select T2D loci containing genes already implicated in diabetes pathophysiology, including PPARG, HNF1A, HNF4A, KCNJ11/ABCC8, and GCKR, or (2) select loci that have undergone elaborate follow-up fine-scale mapping and functional work, including SLC30A8, SLC16A11, and TM6SF2 [15••, 21–27]. This evidence concerns the gene HNF4A and diabetes mellitus.