DEFB103A encodes human β-defensin 3, an antimicrobial peptide with broad-spectrum activity against Gram-positive bacteria (S. aureus, S. pyogenes), Gram-negative bacteria (P. aeruginosa, E. coli), and fungi (C. albicans), including multidrug-resistant pathogens 1. The protein exhibits no significant hemolytic activity and functions through direct bacterial killing mechanisms [UniProt]. DEFB103A expression is regulated by inflammatory signals and epithelial differentiation; it is significantly upregulated in cutaneous infections and psoriasis 12. Estrogen enhances DEFB103A expression in vaginal epithelial cells through estrogen receptor binding to promoter elements, augmenting antimicrobial responses to pathogenic E. coli 3. The gene exhibits substantial copy number variation (2-8 copies per diploid genome) among individuals, potentially contributing to differential infection susceptibility 4. DEFB103A is expressed across multiple barrier tissues including corneal epithelium, conjunctiva, and oral epithelium, where vitamin D3 metabolites enhance its antimicrobial activity 56. In periodontitis, DEFB103A gene modification promotes osteogenic differentiation of periodontal ligament cells through p38 MAPK pathway activation, suggesting therapeutic potential for bone repair 7. These findings indicate DEFB103A functions as a key component of innate immunity at epithelial barriers with implications for infection prevention and tissue repair.