Proopiomelanocortin (POMC) deficiency is a rare genetic disorder with an autosomal recessive inheritance pattern. The disorder is characterized by impaired processing of the POMC protein, which leads to dysfunctional production of different peptides that are involved in the leptin-melanocortin pathway. The main clinical features of the disorder are early-onset obesity, adrenal insufficiency, and hypopigmentation, often presenting as pale skin and red hair or red roots of the hair. The hyperphagia and obesity of people with POMC deficiency can be treated with an MC4R agonist. These patients also need glucocorticoid replacement therapy to treat adrenal insufficiency. Carriers of heterozygous pathogenic loss-of-function variants in POMC often have a higher BMI, but they do not have the complete phenotype of biallelic POMC deficiency.