DEFA3 (defensin alpha 3) is an antimicrobial peptide and key effector of innate immunity that exhibits broad-spectrum activity against bacteria, fungi, and viruses 123. The protein neutralizes bacterial toxins including Bacillus anthracis lethal factor, Clostridium difficile cytotoxin B, and Staphylococcus aureus leukocidin 245. DEFA3 also prevents herpes simplex virus infection by blocking envelope glycoprotein B binding to heparan sulfate receptors 3. The gene exhibits extensive copy number variation (4-11 copies per diploid genome), with approximately 10% of individuals completely lacking DEFA3 6. Population-level variation in DEFA3 absence ranges from 10-37%, suggesting differential innate immune function across populations 7. Clinically, DEFA3 represents a novel bone metabolism-related gene in osteoporosis pathogenesis 8 and inhibits colorectal cancer cell migration and proliferation 9. Paradoxically, increased DEFA1/DEFA3 gene copy number is associated with enhanced sepsis severity through P2X7 receptor-mediated endothelial cell pyroptosis 10. DEFA3 is highly expressed in neonatal megakaryocytes and serves as a developmental biomarker of fetal thrombopoiesis 11.