G protein-coupled receptors (GPCRs, or GPRs) contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins. GPCR GPR6 is a member of this family (subfamily lysophospholipid/lysosphingolipid). GPR6 has been reported to be expressed in brain, particularly in the putamen, and to a lesser extent, in the frontal cortex, hippocampus, and hypothalamus. An EST has been isolated from a human brain (hypothalamus) library. GPCR GPR6 belongs to the G-protein coupled receptor 1 family. It is a receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.