ATP11C is a P4-ATPase that functions as a major phospholipid flippase, catalyzing the ATP-dependent transport of phosphatidylserine (PS) and phosphatidylethanolamine from the outer to inner leaflet of cellular membranes 1. The protein maintains critical membrane asymmetry, particularly in erythrocytes where it prevents PS exposure on the cell surface, which would otherwise serve as a phagocytic signal for splenic macrophage-mediated clearance 1. ATP11C activity is regulated through multiple mechanisms including PKC-mediated endocytosis via a di-leucine motif and caspase-dependent cleavage during apoptosis 2. Mutations in ATP11C cause X-linked congenital hemolytic anemia, with patients showing 10-fold decreased PS internalization and increased senescent cell populations 1. The protein exists in multiple splice variants with distinct subcellular localizations, including polarized membrane distribution in certain cell types 3. Recent studies have implicated ATP11C in cholestatic liver disease as a candidate gene 4 and demonstrated its clinical relevance in sickle cell anemia, where the ATP11C/PLSCR1 ratio correlates with disease severity 5. Structural studies have revealed the detailed mechanism of phospholipid translocation through conformational changes during the transport cycle 6.