In this issue of Genes & Development, Unger and colleagues (doi:10.1101/gad.353153.125) combined human pluripotent stem cell-derived in vitro models with targeted in vivo mouse models to reveal multiple developmental defects triggered by HNF1A mutations causing maturity-onset diabetes of the young. This work paints the picture of a disorder that starts well before diabetes manifests, highlighting its complexity arising from the diverse roles of HNF1A across distinct cell types, each potentially differentially impacted by different mutations.