VGLUT2 Protein is a protein encoded by the [SLC17A6](/genes/slc17a6) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
VGLUT2 Protein is a protein encoded by the [SLC17A6](/genes/slc17a6) gene. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
VGLUT2 (SLC17A6) is a 582-amino acid transmembrane protein that functions as a proton-coupled glutamate transporter into synaptic vesicles. The protein features:
12 transmembrane domains: Characteristic of the major facilitator superfamily
Vesicular lumen orientation: Transports glutamate into the vesicle lumen
Proton gradient coupling: Uses V-ATPase-generated H+ gradient for transport
Oligomerization: Functions as a homodimer
The transporter couples the proton gradient (H+ influx) to glutamate uptake against its concentration gradient.
Normal Function in the Nervous System
VGLUT2 is essential for glutamatergic neurotransmission and vesicle filling:
Glutamate packaging: Packages glutamate into synaptic vesicles for release [1]
Vesicular filling: Determines quantal size of glutamatergic transmission [1]
Synaptic strength: Critical for excitatory synaptic transmission [1]
Brain regional specificity: Highly expressed in thalamus, [cortex](/brain-regions/cortex), brainstem [1]
VGLUT2 is expressed in:
Thalamocortical neurons
Cerebellar granule cells
Brainstem sensory neurons
Subpopulations of cortical pyramidal neurons
Role in Disease
Amyotrophic Lateral Sclerosis (ALS)
VGLUT2 dysfunction is implicated in ALS pathogenesis [2]:
Motor neuron vulnerability: Altered vesicular glutamate transport [3]
Excitotoxicity: Contributes to glutamate excitotoxicity in ALS [2]
Genetic factors: SLC17A6 variants associated with ALS risk [2]
Therapeutic targeting: Modulating VGLUT2 function [3]
Alzheimer's Disease
Glutamatergic dysfunction: Altered VGLUT2 expression in AD brain [4]
Synaptic loss: Contributes to excitatory synaptic deficits [4]