Due to the pleiotropic and multi‐organ metabolic actions of FGF21 and emerging evidence that this hormone mediates the therapeutic effects of currently available drugs and those under development for treatment of metabolic diseases, FGF21 has attracted great interest as a therapeutic target for disorders such as obesity, type 2 diabetes, MAFLD, atherosclerosis, and cardiovascular diseases.[2, 3, 4, 5] Intriguingly, our data suggests that approaches to mildly reduce FGF21 production could be a novel and more efficient strategy to treat obesity and metabolic disorders. The gene discussed is FGF21; the disease is obesity due to melanocortin 4 receptor deficiency.