ATP11B is a P4-ATPase flippase that catalyzes ATP-dependent transport of aminophospholipids, particularly phosphatidylserine and phosphatidylethanolamine, from the outer to inner leaflet of intracellular membranes 1. This activity maintains membrane lipid asymmetry in endosomal compartments 1 and is essential for proper cellular signaling and vesicle trafficking 2. ATP11B shows tissue-specific expression patterns during development, with roles in neural crest, ocular, auditory, and hepatic development 2. Clinically, ATP11B dysfunction is implicated in cerebral small vessel disease (SVD). Loss-of-function mutations cause endothelial cell dysfunction and patchy white matter damage independent of hypertension, suggesting inherent vascular vulnerability 3. However, ATP11B's role in SVD may be population-specific, as variants showed minimal association in Chinese populations 4. In cancer contexts, ATP11B promotes cisplatin resistance in ovarian cancer through enhanced drug efflux via Golgi-to-plasma membrane vesicular transport 5. Conversely, ATP11B upregulation in T cells enhances anti-tumor immunity by increasing S1PR1 externalization, promoting T-cell infiltration into glioblastoma and improving immunotherapy response 6. ATP11B also appears dysregulated in sepsis pathogenesis as an aging-related hub gene associated with immune dysfunction 7.