In contrast to POMC, interestingly, melanocortin-3 and -4 receptors (MC3R, MC4R) that are activated by α-MSH which results from enzymatic cleavage of POMC by prohormone convertase 1, have already been considered promising targets for anti-obesity therapeutics because of their relative specificity for and their central role in energy homeostasis (84). Here, PCSK1 is linked to obesity due to melanocortin 4 receptor deficiency.