The melanocortin 2 receptor (MC2R) accessory protein, MRAP, is one of a small number of G protein-coupled receptor accessory proteins that have been identified in recent years that add control and complexity to G protein-coupled receptor expression and signal transduction. MRAP interacts directly with MC2R and is essential for its trafficking from the endoplasmic reticulum to the cell surface in the adrenal cortex, where it acts as the receptor for the pituitary hormone ACTH. MRAP2, an orthologue of MRAP, is also able to support the cell surface expression of MC2R, although one of its primary sites of action is in the paraventricular nucleus in the hypothalamus. Here it is co-localised with the MC4R and compelling evidence from deletion studies in mice and zebrafish indicate that it has a key role in appetite regulation. The mechanism of action of MRAP and MRAP2 is only beginning to be understood. Recent work has started to reveal some of these mechanisms and the essential domains of MRAP and receptor required for normal function.