A large protein precursor that gets cut up into multiple smaller active peptides — including ACTH, alpha-MSH, and beta-endorphin — depending on which tissue is doing the cutting.241-amino acid precursor cleaved by tissue-specific prohormone convertases (PC1, PC2). In the pituitary anterior lobe: PC1 produces ACTH and β-endorphin. In the intermediate lobe, hypothalamus, and skin: PC2 further cleaves ACTH to produce α-MSH. In the gut: produces β-endorphin and other fragments. Genetic defects in POMC, PCSK1 (encodes PC1), or LEPR (leptin receptor, which regulates POMC neuron activity) impair MC4R signaling downstream and produce severe early-onset obesity — the specific genetic context for setmelanotide’s approval.