SLC38A3 encodes SNAT3, a sodium-coupled neutral amino acid transporter that functions as a symporter cotransporting glutamine, histidine, and asparagine with sodium ions while antiporting protons 1. In the central nervous system, SLC38A3 plays a critical role in the glutamate-GABA-glutamine cycle by transporting L-glutamine from astrocytes to neurons, supporting neurotransmitter synthesis 2. The transport mechanism is electroneutral, pH-dependent, and bidirectional depending on substrate concentration gradients 1. Biallelic SLC38A3 variants cause developmental and epileptic encephalopathy 102, characterized by global developmental delay, intellectual disability, hypotonia, drug-resistant epilepsy, and microcephaly 2. Metabolomic analysis in affected individuals revealed perturbations in glutamate, histidine, and nitrogen metabolism, indicating disease pathophysiology involves glutamine homeostasis disruption 2. Beyond neurological roles, SLC38A3 expression is dysregulated in multiple cancers. In breast cancer, particularly triple-negative breast cancer, SLC38A3 overexpression promotes metastasis via the GSK3β/β-catenin/EMT pathway while reducing oxidative stress 3. In hepatocellular carcinoma, SLC38A3 levels decrease relative to other glutamine transporters, and this decrease predicts worse survival outcomes 4. Conversely, in endometrial cancer, SLC38A3 functions as an oncogene with elevated expression 5. The DEAF1 transcription factor regulates SLC38A3 expression in HCC, promoting glutamine uptake and reducing ROS levels 6.