In the human study, the causal rs1421085 variant resulted in the activation of IRX3 and IRX5 expression during early adipocyte differentiation and a developmental shift from energy-dissipating beige adipocytes to energy-storing white adipocytes [9] and thereby may contribute to the predisposition for obesity, even though the study was restricted to lean healthy adults. Here, IRX5 is linked to obesity due to melanocortin 4 receptor deficiency.