ATP8A1 encodes a P4-ATPase flippase that catalyzes ATP-coupled transport of aminophospholipids, particularly phosphatidylserine (PS), from the outer to inner leaflet of cellular membranes 1. The protein functions as part of a flippase complex with TMEM30A to maintain asymmetric phospholipid distribution across membranes 2. ATP8A1 localizes to multiple intracellular compartments including the trans-Golgi network (TGN), where it interacts with ARF guanine nucleotide exchange factors BIG1 and BIG2 to enhance vesicle coating machinery recruitment 2. The flippase activity regulates cell signaling pathways, including YAP activation through PS concentration in recycling endosomes 3. ATP8A1 is subject to calpain-mediated cleavage during platelet apoptosis, which disrupts membrane asymmetry and enables PS externalization 4. Dysregulated ATP8A1 expression has significant pathological implications: elevated hippocampal levels are associated with autism-spectrum behaviors and altered synaptic connectivity 5, while overexpression protects hepatocytes from ethanol-induced injury via PI3K/Akt signaling 6. Additionally, ATP8A1 expression correlates with obesity-related metabolic changes in adipose tissue 7, suggesting broader roles in metabolic regulation and disease pathogenesis.