This is only the third example in which congenital deficiency of a pro-hormone/peptide processing enzyme has been associated with human disease, the others being PC1/3 in human obesity (which is involved in overlapping endocrine/metabolic pathways) [32], and PCSK9 in autosomal dominant hypercholesterolaemia [44]. Here, PCSK9 is linked to obesity due to melanocortin 4 receptor deficiency.