SLC38A5 is a bidirectional neutral amino acid transporter that mediates sodium-coupled uptake and proton antiport of glutamine, asparagine, serine, glycine, alanine, and histidine across cell membranes. The transporter is expressed in brain, pancreas, intestine, liver, retina, and bone marrow, where it participates in the glutamate-glutamine cycle in neural tissue and glutamine homeostasis in hepatic and retinal tissues. SLC38A5 is markedly overexpressed across multiple cancer types and promotes tumor progression through glutamine-dependent metabolic reprogramming. In pancreatic cancer, SLC38A5 deletion suppresses gemcitabine-resistant cell growth and triggers ferroptosis by reducing glutamine uptake and glutathione synthesis 1. Similarly, in osteosarcoma, SLC38A5 activates the PI3K/AKT/mTOR signaling axis via glutamine transport, promoting cell proliferation and migration while inhibiting ferroptosis 2. In breast cancer, SLC38A5 enhances glutamine metabolism and confers cisplatin resistance 3. In acute lymphoblastic leukemia, both SLC38A5 and ASCT2 mediate asparagine transport essential for blast survival; combined inhibition with V-9302 and GluγHA induces cytotoxicity even in asparaginase-insensitive cells 4. In colorectal cancer, SLC38A5 suppresses ferroptosis via the Hippo-YAP/Nrf2 axis and confers oxaliplatin resistance through ETV4-mediated transcriptional activation 5, 6. Beyond malignancy, SLC38A5 regulates developmental and pathological retinal angiogenesis via Wnt/β-catenin signaling 7, and drives psoriatic inflammation by potentiating lysosomal acidification in dendritic cells, promoting TLR7 activation and IL-23/IL-1β production 8. These findings establish SLC38A5 as a druggable metabolic hub with therapeutic potential in cancer and inflammatory disease.