The EDG (endothelial differentiation gene) family of G protein coupled receptors consists of eight family members that bind lysophospholipid (LPL) mediators, including sphingosine-1-phosphate (SPP) and lysophosphatidic acid (LPA). EDG-1, EDG-3, EDG-5 (also designated H218 and AGR16) and EDG-8 bind SPP with high affinity. EDG-6 is a low affinity receptor for SPP. LPA preferentially binds to EDG-2, EDG-4 and EDG-7. The EDG receptors couple to multiple G proteins to signal through Ras, MAP kinase, Rho, Phospholipase C or other tyrosine kinases, which lead to cell survival, growth, migration and differentiation. EDG-1 signals through Gi proteins to activate Akt and is expressed in glioma cells. EDG-2 is expressed in brain, especially in white matter tract regions, while EDG-3 is expressed in cardiovascular tissue and in cerebellum. EDG-4 is highly expressed on leukocytes and brain, and EDG-5 has wide tissue distribution, including cardiovascular tissue and brain.