PLSCR4 catalyzes rapid, ATP-independent bidirectional movement of phospholipids between the inner and outer leaflets of the plasma membrane in response to metal ion binding, particularly calcium. This phospholipid scrambling activity redistributes phospholipids and participates in multiple cellular processes. In acute respiratory distress syndrome, PLSCR4 alleviates pyroptosis by transporting phosphatidylserine to the external cell membrane, thereby blocking formation of gasdermin D-dependent pores 1. PLSCR4 also regulates adipogenesis through modulation of PI3K/AKT signaling, with reduced expression promoting lipid accumulation in adipose progenitor cells 2. In cancer contexts, PLSCR4 upregulation correlates with malignant progression: it is implicated in colorectal carcinoma proliferation via the miRNA-424-5p feedback loop 3, identified as one of ten TNBC-specific genes 4, and associated with vaso-occlusive crises in sickle cell disease where it promotes erythrocyte membrane deformity 5. In atherosclerosis, PLSCR4 is downregulated in advanced plaques and functions as an M2 macrophage-related gene with potential diagnostic and therapeutic implications 6. The protein shows greatest affinity for calcium over magnesium and zinc. While PLSCR4 participates in disease-relevant processes, its specific therapeutic targeting remains unexplored in the retrieved literature.