SLC16A1 encodes a bidirectional proton-coupled monocarboxylate transporter (MCT1) that catalyzes rapid transport of monocarboxylates including lactate, pyruvate, acetate, and ketone bodies across the plasma membrane 12. Transport direction depends on the proton motive force and substrate concentration gradient, with SLC16A1 functioning as a major lactate exporter 1. The transporter uses alternating conformational states, with protonation of Asp309 essential for this conformational transition 2. SLC16A1 also facilitates succinate export under acidic conditions in exercising muscle and ischemic heart 3. Beyond metabolite transport, SLC16A1 serves as a substrate for gamma-hydroxybutyrate, influencing its pharmacokinetics and tissue uptake 4. Clinically, SLC16A1 mutations cause congenital hyperinsulinemic hypoglycemia (HH), a disease characterized by inappropriate insulin secretion and severe hypoglycemia in neonates and children 5. SLC16A1 mutations account for a minority of diazoxide-responsive HH cases 6. In cancer biology, SLC16A1 promotes pancreatic adenocarcinoma progression by regulating lactate-mediated metabolic signaling, and its exosomal antisense RNA (SLC16A1-AS1) facilitates hepatocellular carcinoma progression through macrophage M2 polarization 78. Additionally, SLC16A1 expression inhibits pancreatic β-cell proliferation and insulin secretion, linking it to type 2 diabetes pathogenesis 9.