ATP8B2 encodes a P4-ATPase flippase that catalyzes ATP hydrolysis coupled to phospholipid transport from the outer to inner leaflet of cellular membranes 1. This enzyme primarily functions as a phosphatidylcholine flippase at the plasma membrane, requiring CDC50A for proper trafficking from the endoplasmic reticulum 2. Beyond phosphatidylcholine, ATP8B2 can also translocate phosphatidylinositol, contributing to phosphoinositide homeostasis and membrane asymmetry maintenance 1. The protein plays crucial roles in cellular processes including autophagy regulation, lysosomal membrane fusion, and mitochondrial homeostasis 34. ATP8B2 downregulation has significant pathological implications, particularly in atherosclerosis where it impairs autophagic flux, inhibits oxidized LDL degradation by macrophages, and exacerbates foam cell formation through disrupted lysosomal function 34. The gene shows disease associations with ulcerative colitis and may influence BMI regulation, with rare loss-of-function variants associated with reduced body mass index 56. Additionally, de novo missense variants in ATP8B2 have been identified in patients with intellectual disability, highlighting its importance in neurological function 2.