SLC16A3 (MCT4) is a proton-dependent transporter of monocarboxylates, particularly L-lactate and pyruvate, expressed on both apical and basolateral plasma membranes 1. The protein contains 12 transmembrane helices and requires association with basigin for proper cell surface expression and activity 1. SLC16A3 plays a predominant role in lactate efflux from highly glycolytic cells, facilitating metabolic adaptation during energy-demanding processes. In skeletal muscle, SLC16A3 exhibits epigenetic memory following high-intensity interval training, with retained hypomethylation and increased expression persisting through detraining periods, contributing to lactate transport capacity 2. In cancer pathology, SLC16A3 emerges as a critical mediator of immunosuppression. Elevated expression correlates with poor prognosis across multiple cancers and reduced CD8+ T-cell infiltration 34. In hepatocellular carcinoma, SLC16A3 overexpression in tumor-promoting macrophages and tumor cells drives immune escape by promoting lactic acid efflux, leading to T-cell dysfunction and exhaustion 5. In intrahepatic cholangiocarcinoma, mutant KRAS cooperatively activates SLC16A3 through the PI3K-AKT-mTORC1-HIF1α pathway, with CK2-mediated phosphorylation at S436 being critical for oncogenic function 6. Pharmacological or genetic SLC16A3 inhibition reduces lactate production, restores anti-PD-1 immunotherapy efficacy, and enhances antitumor immunity 78, positioning SLC16A3 as a promising therapeutic target for immunotherapy-resistant malignancies.