ATP8B1 encodes FIC1, a P4-ATPase flippase that catalyzes ATP-hydrolysis-coupled transport of phospholipids, particularly phosphatidylcholine, from the outer to inner plasma membrane leaflets 1. Beyond lipid transport, ATP8B1 regulates apical membrane protein localization, including CDC42, CFTR, and SLC10A2, and participates in microvillus formation in polarized epithelial cells 2. ATP8B1 also facilitates intestinal absorption of lysophosphatidylcholine (LPC), the primary dietary source of systemic choline 3. Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type 1 (PFIC1), also known as Byler's disease 4. PFIC1 is an autosomal recessive disorder characterized by impaired bile formation and secretion, manifesting in early childhood with jaundice, pruritus, hepatomegaly, and progressive liver fibrosis leading to cirrhosis 5. Twenty to 83% of PFIC patients require liver transplantation, with median survival around 4 years without treatment 6. Beyond cholestasis, ATP8B1 deficiency causes hepatic choline deficiency and steatohepatitis, reversible by choline supplementation 3. Recent evidence reveals ATP8B1 deficiency impairs hepatic gluconeogenesis through phosphodiesterase 4-mediated glucagon resistance 7, indicating broader metabolic dysfunction. Adult-onset ATP8B1 variants associate with chr18 liver disease, though heterozygous carriers may contribute to disease development 8.