XKR8 is a phospholipid scramblase that catalyzes the externalization of phosphatidylserine (PS) on cell membranes through caspase-dependent proteolytic activation 1. During apoptosis, caspase-3 cleaves XKR8 to activate its scramblase activity, enabling irreversible PS exposure on the cell surface as an 'eat me' signal for macrophage-mediated efferocytosis 1. XKR8 functions as a heterocomplex with basigin or neuroplastin chaperone proteins, which facilitate its trafficking to the plasma membrane 2. Beyond apoptosis, XKR8 promotes myoblast differentiation and survival, with overexpression accelerating terminal differentiation and conferring cell-death resistance 3. In the tumor microenvironment, XKR8-mediated PS externalization on apoptotic tumor cells suppresses anti-tumor immunity through PS-receptor interactions with tumor-associated macrophages, promoting immune evasion 4. XKR8 is also incorporated into viral particles, where its scramblase activity promotes PS externalization required for Ebola virus uptake by host cells 5. XKR8 activation can be enhanced by phosphorylation and counteracted by flippase activity 6, revealing sophisticated regulation of PS asymmetry. Blocking XKR8 function represents a potential immunotherapeutic strategy to enhance anti-tumor immunity 7.