POMC (proopiomelanocortin) is a precursor polypeptide that serves as the source of multiple bioactive peptides critical for energy homeostasis and stress response 1. The primary function of POMC involves its tissue-specific processing by prohormone convertases PC1 and PC2 into various peptide products including ACTH, β-lipotropin, α-MSH, β-endorphin, and other melanocortin and opioid peptides 1. In the hypothalamus, POMC neurons function as key appetite-suppressing components of the melanocortin system, responding to leptin and other metabolic signals to regulate food intake and energy expenditure through α-MSH activation of MC4 receptors 23. POMC transcription is tightly regulated through multiple pathways including glucocorticoid feedback, CRH signaling, and developmental transcription factors like Tpit 45. Disease relevance is significant, as POMC mutations cause severe early-onset obesity with adrenal insufficiency and red hair due to disrupted melanocortin signaling 36. Additionally, ectopic POMC expression in tumors can cause Cushing's syndrome through aberrant ACTH production 7. The gene's complex evolutionary history reflects its dual role in both opioid and melanocortin signaling systems 8.