ABCB1 encodes P-glycoprotein, an ATP-dependent efflux pump that translocates drugs and phospholipids across cell membranes. The protein catalyzes translocation of phosphatidylcholine, phosphatidylethanolamine, glucosylceramides, and sphingomyelins from the cytoplasm to the outer membrane leaflet, and mediates energy-dependent drug efflux that reduces intracellular drug accumulation in resistant cells. P-glycoprotein is expressed at the blood-brain barrier, where it protects the brain by extruding substrates including certain antidepressants and antiplatelet agents, and is expressed in skin and intestinal epithelium where it influences drug disposition and absorption. ABCB1 polymorphisms associate with variable treatment responses across multiple therapeutic contexts. In major depression, the rs2032583 SNP shows significant association with antidepressant remission 1. In ischemic stroke patients receiving clopidogrel, the C1236T homozygote wildtype genotype associates with 3.76-fold higher bleeding risk 2. ABCB1 variants influence sufentanil analgesia in pediatric fracture surgery, with CC genotype patients requiring higher doses 3, and contribute to morphine dosing variability, explaining approximately 30% of interindividual differences 4. However, meta-analyses show ABCB1 polymorphisms do not reliably predict chemotherapy response in breast cancer 5 or antiepileptic drug efficacy 6. Genetic variations in ABCB1 associate with disease susceptibility in psoriasis, atopic dermatitis, melanoma, and inflammatory bowel disease 7. ABCB1 inhibitors including valspodar, biricodar, encequidar, and tariquidar have been investigated to reverse drug resistance, though clinical translation remains limited.