Thus, these studies, employing various diets, genetic models and distinct means to silence Ager in a NAFLD-like environment, highlight that RAGE may play adaptive vs. deleterious roles in NAFLD-like conditions, and that more research is needed to dissect cell-intrinsic and cell-cell cross-talk mechanisms in hepatic metabolic dysfunction. Here, AGER is linked to metabolic dysfunction-associated steatotic liver disease.