Phosphatidylinositol45bisphosphat

Phosphatidylinositol 4,5-bisphosphate, commonly abbreviated as PI(4,5)P2 or PIP2, is a minor but essential phospholipid component of the inner leaflet of the plasma membrane. It is a glycerophospholipid with two fatty acyl chains and an inositol headgroup phosphorylated at the 4 and 5 positions. PIP2 serves as a central node in phosphoinositide signaling and interacts with a wide range of proteins that regulate signaling, membrane trafficking, and cytoskeletal dynamics.

Biosynthesis and metabolism of PI(4,5)P2 occur through a two-step phosphorylation of phosphatidylinositol (PI). PI is first converted to phosphatidylinositol 4-phosphate (PI(4)P) by PI 4-kinases, and PI(4)P is then phosphorylated by PI4P 5-kinase to yield PI(4,5)P2. PI(4,5)P2 can be consumed by phospholipase C to generate diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), triggering various downstream responses including calcium signaling. It can also be phosphorylated by PI3K at the 3-position to form PI(3,4,5)P3 or dephosphorylated by phosphatases such as PTEN and 5-phosphatases, returning it to PI(4)P or other inositol phosphates.

Functions of PI(4,5)P2 are diverse. It acts as a substrate for signaling enzymes, participates directly in recruitment and regulation of actin-binding and membrane-trafficking proteins, and modulates the activity of a variety of ion channels and transporters. Through these roles, PI(4,5)P2 influences processes such as endocytosis, exocytosis, vesicle trafficking, and cytoskeletal organization. Dysregulation of PI(4,5)P2 signaling has been linked to multiple diseases, including cancer and neurological disorders.