Proposed functions of MRP4 in mediator storage and drug resistance depending on its localization. (A) Role of MRP4 in mediator storage and release in normal resting and activated platelets. In resting platelets, MRP4 is mainly present in the membrane of dense granules^10,13,14  and mediates sequestration of mediators and possibly other compounds into these organelles (left panel); in activated platelets, MRP4 among other granule membrane proteins is inserted into the plasma membrane on granule exocytosis and may then contribute to the release of a variety of compounds, including de novo generated lipid mediators (right panel). (B) Proposed role of MRP4 in aspirin resistance. As suggested by Mattiello et al,¹⁴  aspirin effect on platelets is little related to MRP4-mediated aspirin transport in normal platelets, although MRP4 may sequestrate a part of the drug into dense granules (left panel). In patients after coronary artery bypass graft surgery, however, MRP4 is up-regulated on the plasma membrane already in resting platelets and mediates active extrusion of aspirin from the cells resulting in an insufficient intracellular COX-1 inhibition by this drug^14,33  (right panel).