MRAP (melanocortin 2 receptor accessory protein) is an essential co-receptor required for the functional expression and signaling of the melanocortin 2 receptor (MC2R), the ACTH receptor in adrenal cells 1. MRAP has a unique antiparallel homodimer structure with dual topology across the cell membrane and performs two distinct functions: facilitating MC2R trafficking to the plasma membrane and enabling ACTH binding and cAMP signaling 2. The protein is absolutely required for MC2R surface expression and ACTH responsiveness, as it forms a stable complex with the receptor 2. Beyond MC2R, MRAP also modulates other melanocortin receptors (MC1R, MC3R, MC4R, MC5R) by enhancing their ligand sensitivity and cAMP generation 3. MRAP expression is regulated by ACTH and angiotensin II in human adrenocortical tissues 4. Mutations in MRAP cause familial glucocorticoid deficiency type 2 (FGD2), accounting for approximately 20% of FGD cases, resulting in ACTH resistance and glucocorticoid deficiency 1. Recent evidence suggests MRAP may also play a role in adipocyte differentiation, particularly in thymic mesenchymal stromal cells during age-related thymic involution 5. The protein's critical role in adrenal steroidogenesis makes it essential for normal glucocorticoid production and stress responses.