Phospholipid-transporting ATPase IC (ATP8B1)

Phospholipid-transporting ATPase IC (ATP8B1) is a critical membrane enzyme of the P4-ATPase family, known as a "lipid flippase." It catalyzes the ATP-dependent translocation of aminophospholipids, especially phosphatidylserine and phosphatidylcholine, from the exoplasmic to the cytosolic leaflet of biological membranes, preserving membrane asymmetry essential for cellular integrity, vesicle formation, protein targeting, and bile secretion. It functions as an obligate heterodimer with CDC50A, a non-catalytic subunit required for ER exit and flippase activity. ATP8B1 is most studied in the liver, where it maintains canalicular membrane integrity during bile acid transport; mutations cause progressive familial intrahepatic cholestasis type 1 (PFIC1) and BRIC1, severe genetic diseases resulting in impaired bile flow and liver dysfunction. ATP8B1 is also critical for vesicular trafficking in other tissues and may have broader roles in cellular homeostasis and disease susceptibility, including possible links to neurodegeneration.

Other names

Familial intrahepatic cholestasis type 1FIC1BRIC1P4-ATPase flippase complex alpha subunit ATP8B1PFIC1probable phospholipid-transporting ATPase ICATPICBRICICP1aminophospholipid transporter class I type 8B member 1E1-E2 ATPase

Drugs influencing ATP8B1 function would likely alter its aminophospholipid flippase activity, affecting the distribution of phosphatidylserine and possibly other phospholipids; perifosine uptake is one described mechanism. Potential restoration or modulation of membrane lipid asymmetry, especially in the context of hepatobiliary diseases.