Multidrug resistance-associated protein 4 (MRP4) (ABCC4)

Multidrug resistance-associated protein 4 (MRP4), encoded by the ABCC4 gene, is a member of the ATP-binding cassette (ABC) transporter superfamily (UniProt P33527). In the kidney, it is localized to the apical membrane of renal proximal tubule cells, where it facilitates the efflux of various organic anions into the tubular lumen for excretion (PubMed: 11483514). Its substrates include endogenous signaling molecules like cAMP, cGMP, and prostaglandins, as well as clinically important drugs such as methotrexate, thiopurines, and antiviral nucleoside analogs (PubMed: 12764137). MRP4 plays a pivotal role in drug disposition and is a key mediator of multidrug resistance in several cancers by pumping chemotherapeutic agents out of tumor cells (PubMed: 15150581). Genetic polymorphisms in ABCC4 are associated with altered drug sensitivity and increased risk of toxicity, particularly nephrotoxicity from drugs like tenofovir (PubMed: 21115055). Understanding MRP4 function is essential for predicting drug-drug interactions and optimizing therapeutic regimens in oncology and infectious diseases.

Other names

ATP-binding cassette sub-family C member 4ABCC4Multi-specific organic anion transporter BMOAT-B

ATP-dependent efflux of substrates across the apical membrane of epithelial cells into the extracellular space or tubular lumen.