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. Most recently, vesicular type transporters for glutamate, termed VGLUTs (VGLUT1/BNPI, VGLUT2/DNPI, and EAT-4), have been cloned and characterized that are related to phosphate transporters. Although neurons exhibit Na-dependent Pi transport, the biological role of Pi uptake is not clear. Proximal tubules in the kidney reabsorb Pi in the glomeruli by the action of a group of phosphate transporters (Type 1-NaPi related, type 2-NaPi-2 related, and type 3-viral receptor-related. These receptors show weak (~20% identity) between various subtypes. A distinct type of brain specific Na+-dependent phosphate (Pi) transporter (BNPI), originally characterized as a plasma membrane transporter has been localized in a subset of glutamatergic neurons (amygdla,cereberal cortex, and hippocmaplus) and identified as VGLUT1 (rat and human 560 aa; ~60kD, ~30% homology with type-1 Pi-transporters & ~75-80% homology with VGLUT2). Interestingly, a sequence induced by subtoxic levels of NMDA in cerebelar granules also belongs to this family of transporters. BNPI/VGLUT1 is expression is restricted to the brain, where it is predominantly located in synaptic vesicles. VGLUT1 shows strong sequence homology (~48%) to EAT-4, a C. elegans protein that appears to have specific presynaptioc role in glutamtergic transmission.