G protein-coupled receptor 50 (GPR50), previously known as the melatonin-related receptor, share 45% sequence identity to melatonin receptors MT1 and MT2 but it does not bind melatonin or any other known ligand and therefore remains an orphan receptor without a clear function^1,2.

GPR50 belongs to the G protein coupled receptors (GPCRs) family, a large group of receptors characterized by seven trans membrane helices that transmit a signal from the outside cellular surface into the inside of the cell through conformational changes. GPCRs mediate most of the physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases¹.

GPR50 was identified as a risk gene for bipolar disorder and major depression and it was shown to have a role in neural development and sterol metabolism, it was also shown to be related to mood disorders, adaptive thermogenesis and torpor response (the body's response to starvation)².

 In addition, it was shown to have a dramatic effect on neurite outgrowth, supporting a likely role in neural development and it was also found to be expressed in various types of cancer³.

GPR50 is expressed in the pituitary, hypothalamus, cortex, midbrain, pons, amygdala, and in several brainstem nuclei^3,4. 

Due to its involvement in a wide range of mental conditions and disease, GPR50 is a major target for research and drug development.