PLSCR4 (phospholipid scramblase 4) catalyzes metal ion-induced, ATP-independent bidirectional movement of phospholipids between plasma membrane leaflets 1. The protein exhibits greatest affinity for calcium ions, which bind to calcium-binding sites and induce conformational changes enabling phospholipid redistribution 1. Mechanistically, PLSCR4 regulates multiple cellular processes through distinct pathways. In inflammation, PLSCR4 attenuates pyroptosis by translocating phosphatidylserine to the outer membrane, blocking gasdermin D pore formation and reducing IL-1β and IL-18 release in lipopolysaccharide-induced acute respiratory distress syndrome 2. In adipose tissue, PLSCR4 suppresses adipogenesis by antagonizing PI3K/AKT signaling through PIP3 regulation, with PLSCR4 most highly expressed in human adipose tissue relative to other scramblases 3. Clinically, PLSCR4 dysregulation associates with multiple pathologies. Expression increases approximately 6-fold during sickle cell vaso-occlusive crises, serving as a potential biomarker by promoting erythrocyte membrane deformity and hemolysis 4. PLSCR4 upregulation contributes to colorectal cancer progression through miRNA-424-5p feedback mechanisms 5, while downregulation in atherosclerotic plaques suggests involvement in M2 macrophage-mediated plaque regression 6. PLSCR4 also appears dysregulated in triple-negative breast cancer and myocardial hypertrophy 78.