Melanocortin-2 receptor accessory protein (MRAP)

Melanocortin-2 receptor accessory protein (MRAP) is a small, single-pass transmembrane protein that forms antiparallel homodimers with a unique dual topology—both its N- and C-termini can be oriented extracellularly. MRAP is absolutely required for the functional expression of the melanocortin-2 receptor (MC2R, or ACTH receptor): it traffics MC2R from the endoplasmic reticulum to the plasma membrane, enabling receptor glycosylation, ACTH binding, and downstream signaling via cAMP. Without MRAP, MC2R is retained in the ER and fails to respond to ACTH, resulting in familial glucocorticoid deficiency. MRAP expression is found in adrenal cortex, lymph nodes, brain, testis, breast, thyroid, and adipose tissue, and is regulated by ACTH and other signals. It is not itself a classical receptor, enzyme, or drug target but is indispensable for MC2 receptor function, making it a critical molecular chaperone and accessory protein.

Other names

C21orf61FALPB27MRAP1Fat cell-specific low molecular weight proteinFat tissue-specific low MW proteinFGD2GCCD2

Not directly drug-targeted; essential for MC2 receptor function, which mediates ACTH-induced cAMP signaling