scramblase

A scramblase is a membrane protein that catalyzes the transbilayer movement of phospholipids across the lipid bilayer, thereby dissipating the typical lipid asymmetry of cellular membranes. Unlike ATP-dependent flippases and floppases, scramblases generally operate without direct energy input, and many are activated by calcium or by signaling events such as apoptosis.

Major scramblase families include the TMEM16/ANO family, which contains calcium-activated scramblases such as TMEM16F that reside in the plasma membrane and promote outward exposure of phospholipids like phosphatidylserine. The XKR family comprises caspase-activated scramblases (notably XKR8) that drive phospholipid scrambling during apoptosis. The phospholipid scramblase (PLSCR) family, including PLSCR1, consists of calcium-dependent scramblases implicated in lipid translocation and signaling; however, their exact mechanisms and physiological roles are diverse and still under study.

Physiological roles of scramblases include signaling during apoptosis through exposure of phosphatidylserine, which marks cells for phagocytosis; participation in coagulation on activated platelets; and various membrane remodeling processes. Scramblases help regulate or rapidly alter lipid distribution in membranes during processes such as cell signaling, vesicle formation, and stress responses. While most research emphasizes plasma membrane activity, scramblases can also influence lipid organization in other cellular membranes.