Vesicular glutamate transporter 2

Vesicular glutamate transporter 2 (VGluT2), encoded by SLC17A6, is a multifunctional transporter localized to synaptic vesicles that mediates L-glutamate uptake from the cytoplasm into presynaptic terminals of excitatory neurons (UniProt: Q9P2U8). Beyond its primary glutamate uniporter function, VGluT2 also transports phosphate and functions as a chloride channel and potassium/proton antiporter, collectively maintaining the ion gradients necessary for vesicular acidification and sustained glutamate accumulation. At the plasma membrane, it functions as a sodium-phosphate symporter involved in synaptic phosphate homeostasis.

VGluT2 is predominantly expressed in excitatory neural tissues and plays a critical role in glutamatergic neurotransmission at the synapse (UniProt: Q9P2U8). The protein is also involved in retinal vessel development and may participate in endocrine glutamatergic signaling in tissues such as the pineal gland and pancreas.

VGluT2 is downregulated in Alzheimer's Disease brain tissue. Chaparral AD proteomics data from post-mortem human AD brain compared to age-matched controls shows a mean log2 fold-change of −0.50, indicating reduced expression levels across the analyzed subcellular fractions. This downregulation may reflect compromised glutamatergic synaptic function characteristic of AD pathology.