Membrane remodeling in normal and Scott cells. In the plasma membrane, dynamic maintenance or loss of asymmetric phospholipid distribution results from opposite fluxes under the control of specific transporters governing inward (flip) or outward (flop) translocation. In the resting membrane, the flippase activity of aminophospholipid translocase is prominent and subtained (left, yellow ellipse). Thus, aminophospholipids, phosphatidylserine (PS; red negative polar heads), and phosphatidylethanolamine (PE; open polar heads) are sequestered into the inner leaflet. Following stimulation, specific vectorial floppase and/or nonspecific bidirectional scramblase activities are rapidly turned on, and PS and PE are moved to the outer leaflet (upper right). Flippase activity is shut down, leading to transient mass imbalance between the two leaflets. Membrane blebbing ultimately resolves into microvesicle or microparticle (MP) shedding after cytoskeleton degradation by calcium-dependent proteolysis. Stimulated cell membrane and MP therefore expose PS, which is particularly crucial in platelet procoagulant response for the calcium-dependent assembly of the cascade of clotting enzyme complexes. The assembly of these complexes, composed of an enzyme (E) and a cofactor (C) in the activation of a substrate (S), culminates in the generation of sufficient thrombin for efficient hemostasis. In resting Scott cells, flippase activity is indeed operational; stimulation remains without effect on the swift induction of floppase and/or scramblase and consecutive membrane shedding, explaining the resulting hemorrhagic phenotype (lower right). During the slower process of apoptotic cell death, however, PS egress is normal in Scott cells. As yet, floppase candidates have remained elusive.