ABCC4 is an ATP-dependent transporter of the ABC family that actively extrudes diverse endogenous compounds and xenobiotics from cells 1. Its primary substrates include cyclic nucleotides (cAMP and cGMP), bile acids, prostaglandins, urate, and glutathione conjugates such as leukotrienes 23. ABCC4 also transports anticancer, antiviral, and antibiotic drugs, conferring resistance to agents like methotrexate 1. Mechanistically, ABCC4 functions within macromolecular complexes: it physically couples with CFTR in airway epithelial cells to regulate cAMP signaling 4, and PKA activation assembles a PDZ-dependent protein network that stabilizes ABCC4 at the cell surface and optimizes cAMP efflux 5. ABCC4 mediates transport of platelet agonists and antagonists, suggesting relevance to hemostasis and thrombosis 6. Clinically, ABCC4 polymorphisms affect drug resistance; the G187W variant reduces SN-38 resistance 7. Recent evidence identifies ABCC4 as a regulator of LDL cholesterol clearance through cAMP-dependent suppression of PCSK9, linking ABCC4 inhibition to potential atherosclerosis therapeutics 8. Species differences in ABCC4 substrate selectivity—notably human ABCC4 transports arsenic metabolites while mouse Abcc4 does not—may explain toxicokinetic variations between organisms 9.