SLC38A3 encodes SNAT3, a sodium-coupled neutral amino acid transporter that mediates cotransport of L-glutamine, L-histidine, and L-asparagine with sodium ions, coupled to proton antiport. In the brain, it functions as the principal transporter in the glutamate-GABA-glutamine cycle, facilitating glutamine uptake by neurons and supporting replenishment of the neurotransmitters glutamate and GABA. The transporter also regulates amino acid homeostasis and nitrogen metabolism. Biallelic SLC38A3 variants cause developmental and epileptic encephalopathy 102, characterized by global developmental delay, intellectual disability, hypotonia, and drug-resistant epilepsy in approximately half of affected individuals 1. Metabolomic analysis in affected subjects reveals perturbations in glutamate, histidine, and nitrogen metabolism, suggesting disease pathophysiology involves disrupted glutamine homeostasis 1. In cancer contexts, SLC38A3 plays distinct roles: it promotes breast cancer metastasis via the GSK3β/β-catenin/EMT pathway 2, while in hepatocellular carcinoma and endometrial cancer, elevated SLC38A3 expression correlates with worse survival outcomes and enhanced glutamine-dependent metabolic reprogramming [PMID:39062801; 38]. A recent study demonstrates that oncogenic DEAF1 transcription factor elevates SLC38A3 expression to reduce oxidative stress and promote HCC progression 4. Additionally, SLC38A3 genetic variants associate with type 2 diabetes risk 5.