SLC22A6 (OAT1) functions as a Na+-independent organic anion transporter that facilitates the cellular uptake of organic anions coupled with efflux of intracellular dicarboxylates like α-ketoglutarate 1. Located primarily at the basolateral membrane of renal proximal tubule cells, SLC22A6 mediates the first step in renal elimination of diverse organic anions from blood to urine 1. The transporter handles endogenous substrates including prostaglandins, cyclic nucleotides (cAMP, cGMP), and neuroactive tryptophan metabolites 1. It also transports uremic toxins such as indoxyl sulfate and xenobiotics like ochratoxin A, contributing to detoxification 1. Recent evidence shows SLC22A6 can transport the thyroid hormone analog TRIAC, suggesting broader physiological roles 2. In pathological contexts, SLC22A6 contributes to atherosclerosis by enhancing glycolytic metabolism and lactate uptake in endothelial cells, leading to histone H3K9 lactylation and endothelial dysfunction 3. Genetic polymorphisms in SLC22A6, particularly rs1158626, occur at higher frequencies in African populations and affect drug pharmacokinetics, including increased affinity for antiretroviral drugs 4. The transporter also shows significant expression differences across species, with higher levels in mouse brain microvessels compared to human and monkey 5.