flippase

Flippase is a term used for enzymes that move phospholipids from the outer (exoplasmic) leaflet of a biological membrane to the inner (cytosolic) leaflet, helping to maintain membrane lipid asymmetry essential for cell function.

In eukaryotes, flippases primarily belong to the P4-ATPase family of P-type ATPases. They couple ATP hydrolysis to translocation of specific phospholipids, most notably aminophospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), from the extracellular toward the cytosolic leaflet. Activity often requires accessory subunits in the CDC50 family that assist in trafficking and substrate specificity. Examples include human ATP8A1, ATP8A2, ATP11A, ATP11B, and ATP11C, as well as the yeast Drs2p in complex with Cdc50p.

Flippases operate in contrast to scramblases, which randomize phospholipid distribution without requiring energy, and to floppases, which move lipids in the opposite direction. Proper flippase function is important for membrane biogenesis and vesicle trafficking, and for signaling processes that depend on leaflet composition. Disruptions in flippase activity have been linked to human diseases in some cases; for example, mutations in ATP8B1 (a PS/PE flippase) are associated with familial intrahepatic cholestasis, while other flippases contribute to immune and developmental functions.

Overall, flippases play a key role in preserving membrane asymmetry and enabling membrane-related processes across diverse organisms.