{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC22A2, which encodes the organic cation transporter 2 (OCT2), is a membrane carrier predominantly expressed in renal proximal tubular cells. It plays a central role in the uptake and secretion of endogenous organic cations such as creatinine, amino acids, and other metabolites, thereby contributing to renal clearance. Genetic analyses have revealed multiple variants that affect OCT2’s transport activity and expression, underscoring its importance in normal renal function and in the variation of serum biomarkers used to assess kidney function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its endogenous substrates, OCT2 mediates the cellular uptake of several xenobiotics and therapeutic drugs. Its transport function is critical for the renal handling of platinum‐based anticancer agents such as oxaliplatin, cisplatin, and picoplatin – thereby modulating both antitumor efficacy and drug‐induced nephrotoxicity. Similarly, OCT2 is implicated in the pharmacokinetics of metformin and in the transport of other organic cations including agmatine, ranitidine, rhodamine 123, as well as key biogenic amines such as asymmetric dimethylarginine and L‐arginine. Studies demonstrate that common genetic polymorphisms in SLC22A2 can alter OCT2 transport activity, contributing to individual differences in drug disposition, efficacy, and side effect profiles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOCT2 function is further modulated by post‐translational modifications, oligomerization, and transcriptional as well as epigenetic regulatory mechanisms, which can affect its plasma membrane targeting and transport kinetics. Such regulation not only influences the susceptibility to drug-induced toxicities (for example, cisplatin nephrotoxicity) but also appears to impact chemoresistance profiles in cancer, with changes in OCT2 expression being linked to altered intracellular drug accumulation. Moreover, several studies have implicated microRNA-mediated regulation and promoter polymorphisms as factors altering OCT2 expression levels, thereby contributing to inter‐individual variations in both drug response and adverse event risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maya K Leabman, Conrad C Huang, Michiko Kawamoto, et al. 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