While it remains controversial as to whether the obesity-related SNPs in FTO act via modulation of FTO function or by influencing adjacent genes such as IRX3 and RPGRIP1L, our results provide firm evidence that FTO modulates adipogenesis, and thereby fat mass, both in vitro and in vivo. The gene discussed is RPGRIP1L; the disease is obesity due to melanocortin 4 receptor deficiency.