MFGE8 (Milk Fat Globule-EGF Factor 8) is a secreted glycoprotein that functions as a critical regulator of cellular interactions and tissue homeostasis through multiple mechanisms. The protein serves as a phagocytic modulator, facilitating efferocytosis (clearance of apoptotic cells) by binding to phosphatidylserine on dying cells and bridging them to phagocytes via integrin receptors 1. In the central nervous system, astrocyte-derived MFGE8 promotes microglial synapse elimination in Alzheimer's disease, contributing to pathological synapse loss 23. The protein demonstrates tissue-protective properties in some contexts, preventing intestinal fibrosis by inhibiting extracellular matrix production through integrin αvβ5 and focal adhesion kinase signaling 4. However, MFGE8 also exhibits pathological roles, acting as a metastatic trophic factor secreted by vertebral skeletal stem cells that contributes to bone metastasis 5. Additionally, MFGE8 promotes immunotherapy resistance by enhancing PD-L1 sorting onto tumor-derived extracellular vesicles through αv integrin signaling and UBE4A upregulation 6. The protein shows therapeutic potential, as MFGE8-containing nanoparticles can transform macrophages from pro-inflammatory to anti-inflammatory phenotypes in liver fibrosis treatment 7. Genetic studies identify MFGE8 as a potential therapeutic target for sarcopenia, where upregulation correlates with improved muscle mass 8.