BPIFA1 (BPI fold containing family A member 1) is a secretory lipid-binding protein with primary specificity for surfactant phospholipid DPPC 1 that functions as a key component of innate immune defense in mucosal tissues. Mechanistically, BPIFA1 reduces surface tension in airway secretions and inhibits biofilm formation by pathogenic Gram-negative bacteria including Pseudomonas aeruginosa and Klebsiella pneumoniae 23. Additionally, BPIFA1 negatively regulates proteolytic cleavage of SCNN1G, thereby preventing inappropriate ENaC activation and maintaining airway surface liquid homeostasis 45. Gene expression marks epithelial differentiation during mucociliary development 6, and BPIFA1 expression is documented across upper airway tissues including nasal cavity, sinuses, and middle ear 78. Disease relevance is significant: reduced BPIFA1 expression associates with asthma severity and greater eosinophilic inflammation, particularly in patients carrying the rs750064 CC genotype 9. BPIFA1 regulates anti-inflammatory macrophage polarization and suppresses NF-κB signaling in periodontitis 10. Novel antimicrobial peptides derived from BPIFA1 demonstrate antifungal activity against Candida albicans 11. Clinically, salivary BPIFA1 levels increase during head and neck cancer radiotherapy, correlating with mucositis severity 12. Emerging evidence suggests BPIFA1 as an immunotherapeutic target for inflammatory airway diseases.