Slc17a6, also known as Vglut2, is a gene encoding a vesicular glutamate transporter. It endows specific neuronal cell types with the ability to use glutamate as a neurotransmitter, playing a crucial role in glutamatergic neurotransmission, which is vital for normal nervous system function [1].

In mouse models, reduced Vglut2/Slc17a6 gene expression levels throughout the subthalamic nucleus (STN) led to cell loss and structural disorganization, followed by increased motor activity and decreased sugar consumption. This indicates its role in regulating motor and reward-related functions [3]. Conditional knockout of CPEB2 in VGLUT2-expressing glutamatergic neurons impaired consolidation of hippocampus-dependent memory in mice, suggesting Slc17a6 is involved in memory-related glutamatergic transmission and presynaptic plasticity [4]. Knocking out the glutamate transporter VGLUT2 from enkephalin neurons disrupted gastrointestinal transit, positing glutamatergic neurons regulated by Slc17a6 as key interneurons in intestinal motility [5].

In conclusion, Slc17a6 is essential for glutamatergic neurotransmission. Model-based research, especially through KO/CKO mouse models, has revealed its significant roles in motor, reward-related, memory, and intestinal motility processes. These findings contribute to understanding related disease mechanisms such as in Parkinson's disease where sex-specific PD-associated methylation changes in SLC17A6 have been reported [2].