Glutamate is the main excitatory neurotransmitter in the brain. To date five glutamate Transporters have been cloned: GLAST (EAAT1), GLT1 (EAAT2), EAAC1 (EAAT3), EAAT4 and EAAT5. These transporters are believed to be critical in reducing potentially toxic extracellular concentration of glutamate by rapid uptake into nerve terminals and glial cells. Glutamate transporters (525-573aa) display about 55% homology. They are predicted to contain up to 6-10 transmembrane domains. Immunolocalization studies indicate that GLT1 is localized in astroglial cells throughout the brain and spinal cord. EAAC1 is specific for certain neurons and Purkinje cells. It is specifically enriched in cortex, hippocampus and caudate-putamen. It is confined to presynaptic and postsynaptic elements. GLAST has been observed in both neuron and astroglia. It is most abundant in Bergmann glia, cortex, hippocampus and cerebellum. EAAT4 has properties of ligand gated Cl-channel. It is localized mainly in cerebellar Purkinje cells in rat and human CNS. EAAT5 has only been cloned from human. It is primarily expressed in retina. GLAST (sodium dependent Glutamate/Aspartate Transporter 1, or Excitatory Amino Acid Transporter 1, EAAT1) is a glutamate transporter. It is a transmembrane protein with ~543aa and a molecular weight of 67kD.