BPIFB2 (BPI fold containing family B member 2) is a secreted antimicrobial protein belonging to the bactericidal/permeability-increasing (BPI) fold-containing family, localized to the extracellular region and endoplasmic reticulum lumen 1. The protein functions as part of the innate immune defense system, with expression predominantly in serous glandular cells of mucosal tissues 2. Mechanistically, BPIFB2 expression is downregulated in various pathological conditions. In chr20 rhinosinusitis with nasal polyps (CRSwNP), BPIFB2 levels are significantly reduced alongside other antimicrobial proteins, correlating with decreased submucosal gland numbers 3. Similarly, BPIFB2 is downregulated in oral squamous cell carcinoma salivary samples and in primary Sjögren's syndrome 4, 1. Expression is further suppressed in schizophrenia and gastrointestinal disorders, where it may contribute to immune dysfunction 5, 6. Clinically, reduced BPIFB2 expression serves as a potential biomarker for disease diagnosis and prognosis. In OSCC, BPIFB2 downregulation contributes to diagnostic biomarker panels with 94% AUC for early-stage disease detection 4. BPIFB2 is also integrated into prognostic scoring systems for intrahepatic cholangiocarcinoma, where its expression correlates with cancer-associated fibroblast infiltration and unfavorable survival outcomes 7. Glucocorticoid treatment increases BPIFB2 expression, suggesting therapeutic potential in inflammatory airway diseases 2.