The cyclic neuropeptide, Melanin-Concentrating Hormone (MCH), plays an important role in food intake and energy balance. MCH stimulates feeding, it is up regulated in obese mice and in fasting. Animals lacking MCH eat less and are lean. Most recently, a receptor for MCH (MCHR) has been cloned and characterized. Human MCH receptor is 402-aa membrane protein. It is also described as an orphan G-protein coupled receptor SLC-1 or GPR24, somatostatin receptor-like protein. It has 7 transmembrane domains, a Dry motif at the boundary of TM3 and the 2nd intracellular loop, a consensus site for N-linked glycosylation at the N-terminus. MCHR is expressed in ventromedial and dorsomedial nuclei of the hypothalamus. Recently, an orphan G-protein coupled receptor (SLC-1,GPR24) has been identified as the receptor of MCH. MCH receptor (MCH1R; human 402 aa, rat 353 aa) is predicted to contain 7 transmembrane domains, a feature typical of G-protein coupled receptors. It is primarily expressed in the ventromedial and dorsomedial nuclei of the hypothalamus. Moderate levels of MCHR are also found in the eye and skeletal muscle, tongue, and pituitary. MCHR binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca and reduce forskolin-elevated cAMP levels. Recently, a novel second human MCH receptor (MCH2R) has been cloned and characterized. MCH2R gene encodes a 340 aa protein with 38% identity with MCH1R. It has the basic characteristics of GPCR and belongs to class 1 (rhodopsin-like) GPCR superfamily. MCH2R transfected cells responds to MCH with an increase in intracellular Ca+2 levels, and increased cellular extrusion of protons. MCH2R is mainly expressed in the brain.