We also report two haploinsufficient individuals with peripheral lipodystrophy, and centripetal obesity with dyslipidemic severe insulin resistance, and two less well studied individuals with severe insulin resistance and rare missense variants in ARL15. Neither haploinsufficient patient had adiponectin levels or oligomeric profiles that were distinct from control volunteers with primary lipodystrophy or hyperandrogenemic, insulin resistant PCOS. Here, ARL15 is linked to obesity due to melanocortin 4 receptor deficiency.