SLC22A3 encodes organic cation transporter 3 (OCT3), an electrogenic, voltage-dependent transporter mediating bidirectional transport of organic cations including endogenous monoamine neurotransmitters and xenobiotics 123. Transport is driven by electrochemical potential independent of Na+ and Cl- gradients 23. SLC22A3 transports dopamine, serotonin, histamine, noradrenaline, and epinephrine, supporting aminergic neurotransmitter homeostasis in the brain 145. The transporter also handles polyamines (spermidine, putrescine, agmatine) and contributes to renal clearance of cationic compounds 23. In astrocytes, neuronal activity induces SLC22A3 expression, regulating serotonin uptake and histone serotonylation to control GABA release and sensory processing 6. SLC22A3-mediated histamine uptake suppresses cholangiocarcinoma proliferation by facilitating histamine degradation 7. Conversely, high SLC22A3 expression associates with poor lung squamous cell carcinoma prognosis through enhanced inflammatory responses 8. In colorectal cancer, SLC22A3-dependent serotonin uptake drives histone serotonylation in cancer-associated fibroblasts, promoting tumor progression 9. SLC22A3 polymorphisms show associations with cardiovascular disease risk and warfarin sensitivity, with rs10455872 correlating with warfarin responsiveness 101112.