MC2R is a G protein-coupled receptor that serves as the primary ACTH (adrenocorticotropin) receptor, predominantly expressed in the adrenal cortex where it regulates adrenocortical function 1. Upon ACTH binding, MC2R couples to Gs protein and activates adenylate cyclase, stimulating the cAMP-dependent signaling pathway, MAPK cascade, and PKA pathway, which converge on steroidogenic factor 1-mediated transcriptional activation 1. This signaling cascade directly mediates the release of adrenal glucocorticoids including cortisol and corticosterone 2. MC2R function requires the melanocortin receptor accessory protein (MRAP) for proper cell surface expression and ACTH binding; mutations in either MC2R or MRAP cause familial glucocorticoid deficiency (FGD), an autosomal recessive disorder characterized by ACTH insensitivity 3. MC2R mutations account for approximately 25% of FGD type 1 cases 3, while MRAP mutations account for 20% of FGD type 2 cases 3. Beyond adrenal function, MC2R is expressed in ocular tissues where it participates in immune regulation, though pharmacological targeting of other melanocortin receptors is preferred therapeutically to avoid MC2R-mediated corticosteroid production 4.