Flippase

Flippases are a family of transmembrane lipid transporter proteins that facilitate the movement of phospholipids from one leaflet of a cell membrane to the other. This process, known as "lipid flipping" or "transbilayer movement," is crucial for maintaining membrane asymmetry, regulating cell signaling, and facilitating various cellular processes.

Unlike scramblases, which catalyze bidirectional and non-specific lipid movement leading to a more randomized distribution, flippases generally exhibit specificity for certain types of phospholipids and directionality. Specifically, they typically move phospholipids from the exoplasmic (outer) leaflet to the cytosolic (inner) leaflet of the cell membrane. This ATP-dependent process maintains the concentration of certain lipids, such as phosphatidylserine (PS) and phosphatidylethanolamine (PE), in the inner leaflet, which is vital for cellular signaling pathways, apoptosis, and blood coagulation.

The term "flippase" originally referred to any enzyme facilitating the transbilayer movement of lipids. However, with a better understanding of the proteins involved, the term is now generally applied to specific ATP-dependent transporters, particularly those belonging to the P4-ATPase family. These P4-ATPases form complexes with accessory proteins, such as CDC50 proteins, which are essential for their proper function and localization.

Dysfunction of flippases has been implicated in various diseases, including neurological disorders, cancer, and bleeding disorders, highlighting their importance in maintaining cellular homeostasis. Further research into the mechanisms and regulation of flippases is ongoing, aiming to better understand their roles in health and disease.