Since naturally occurring mutations and the targeted disruption of genes in mouse models (Lep, Lepr, Pomc, Mc4r, and Mc3r) were all found to have key roles in the same molecular pathway, genes in and associated with the leptin/melanocortin pathway became logical candidates to consider in clinical cases where obesity remained unexplained. Here, POMC is linked to obesity due to melanocortin 4 receptor deficiency.