SLC43A2 encodes LAT4, a facilitated diffusion transporter that mediates uptake of L-phenylalanine, L-methionine, and branched-chain amino acids (including L-leucine and L-isoleucine) across cell membranes in a sodium- and chloride-independent manner. The transporter is expressed at the blood-brain barrier and plays a role in transepithelial amino acid absorption in kidney and small intestine. In the central nervous system, SLC43A2-mediated L-leucine transport contributes to amino acid homeostasis at the blood-brain barrier alongside other facilitative and sodium-dependent transporters 1. SLC43A2 has emerged as a critical node in cancer immunometabolism. Tumor cells upregulate SLC43A2 to compete with CD8+ T cells for methionine, depleting the methyl donor S-adenosylmethionine and reducing histone H3K79 dimethylation, thereby suppressing STAT5 expression and impairing T cell immunity 2. Similar mechanisms operate in acute myeloid leukemia, where SLC43A2 overexpression correlates with reduced CD8+ T, NK, and B cell infiltration and poorer survival 3. In esophageal squamous cell carcinoma, SLC43A2 inhibition cooperates with methionine restriction to trigger ferroptosis through a feedback loop with NFκB signaling 4. SLC43A2 also sustains YAP-mediated drug resistance through methionine-dependent protein methylation 5. Emerging therapeutic approaches include BCH-mediated SLC43A2 inhibition, methionine supplementation to restore T cell function, and Norathyriol, which targets circPETH-147aa-driven SLC43A2 upregulation in hepatocellular carcinoma to enhance anti-PD1 efficacy 6. Outside malignancy, SLC43A2 methylation serves as a predictive biomarker for chr17 kidney disease development in type 2 diabetes 7.