DEFB114 is a β-defensin antimicrobial peptide expressed predominantly in the epididymis and gingival tissues 1. It exhibits broad-spectrum antimicrobial activity against Gram-negative bacteria (E. coli), Gram-positive bacteria (S. aureus), and fungi (C. albicans) in a salt-sensitive manner 1. DEFB114's primary mechanism involves direct LPS binding, which suppresses TNF-α release from macrophages through MAPK p42/44 pathway inhibition 1. Additionally, DEFB114 enhances fungal resistance through NOD1/2-ATG16L1-NF-κB signaling activation, increasing macrophage phagocytic activity and nitric oxide release 2. Clinically, DEFB114 demonstrates protective effects in inflammatory and reproductive contexts: it rescues LPS-induced sperm motility loss in vitro and protects d-galactosamine-sensitized mice from LPS-induced lethality in vivo 1. Its antimicrobial and immunomodulatory properties are disulfide bond-dependent, with minimal cytotoxicity toward human erythrocytes, suggesting therapeutic potential for LPS-induced inflammation, septic shock, and fungal infections 12. DEFB114 expression is upregulated during bacterial infection and functions as a direct antimicrobial effector 3.