SLC17A6 encodes a vesicular glutamate transporter (VGLUT2) that functions as a multifunctional transporter at synaptic vesicle membranes. Its primary role is to package L-glutamate into synaptic vesicles at presynaptic terminals of excitatory neurons, driven by the proton electrochemical gradient established by vacuolar H+-ATPase 1. The transporter also mediates phosphate and chloride ion transport, with K+/H+ antiporter activity maintaining the electrical gradient necessary for sustained glutamate uptake 1. At the plasma membrane following exocytosis, SLC17A6 functions as a Na+/phosphate symporter regulating synaptic phosphate homeostasis 2. Clinically, SLC17A6 dysfunction is implicated in multiple neurological disorders. It is identified as a hub gene in early Alzheimer's disease, specifically linked to synaptic abnormalities 3. SLC17A6 expression changes are also detected in schizophrenia, particularly within GABAergic and excitatory neuronal subpopulations in the ventral midbrain 4. Genetic variants in SLC17A6 show gene-by-smoking interactions affecting Parkinson's disease susceptibility 5, and reduced SLC17A6 expression in the subthalamic nucleus causes motor and reward-related behavioral alterations with mesostriatal dopamine system dysfunction 6. Additionally, SLC17A6 dysfunction is associated with encephalo-dysplasia through altered N-glycosylase expression and endoplasmic reticulum stress 7.