Our results suggest that indirect activation of hepatic GCK via loss-of-function GCKR mutations does not consistently lead to a hyperlipidemic phenotype, and are particularly relevant to the recent report of a selective small-molecule inhibitor of GKRP, which was shown to disrupt the GCK–GKRP interaction in vivo and reduced blood glucose levels in mouse models of obesity without apparent adverse effects on triglyceride levels (25). The gene discussed is GCKR; the disease is Obesity.