{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC22A1, which encodes the organic cation transporter 1 (OCT1), is a pivotal membrane protein principally expressed in hepatocytes where it mediates the uptake of a wide spectrum of endogenous and exogenous organic cations. Detailed functional analyses in heterologous systems have revealed that OCT1 handles numerous substrates—ranging from drugs to monoamine neurotransmitters—and is also expressed in extrahepatic sites such as the placenta and airway epithelia, thereby contributing to both drug absorption and local physiological functions. Moreover, studies involving systematic mutation screening and signaling‐pathway modulation have underscored the transporter’s polyspecificity and its sensitivity to genetic and regulatory influences."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical investigations have demonstrated that OCT1 plays a central role in dictating the therapeutic efficacy and pharmacokinetics of several drugs. For instance, reduced OCT1 activity—often due to nonsynonymous genetic variants—diminishes the hepatic uptake of metformin, thereby attenuating its glucose‐lowering effects in type 2 diabetes, and similarly influences the intracellular accumulation and overall response to tyrosine kinase inhibitors (e.g., imatinib) in chronic myeloid leukemia. Such pharmacogenetic studies consistently show that interindividual variability in OCT1 function correlates with altered plasma drug concentrations, modified clinical outcomes, and even varying adverse event profiles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its established role in modulating the response to antidiabetic and anticancer agents, emerging data indicate that OCT1 crucially influences the disposition of other therapeutic and endogenous agents. Its activity affects the uptake of novel anticancer drugs such as picoplatin and tropisetron, underlies the hepatocellular efflux of acylcarnitines and thiamine—thereby impacting energy metabolism—and contributes to the pharmacokinetic variability observed with opioids like morphine. 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