BPIFB1 (BPI fold containing family B member 1) is a secreted protein primarily functioning in innate immunity of respiratory and mucosal tissues. It binds bacterial lipopolysaccharide and modulates toll-like receptor 4 signaling 1, with documented immunomodulatory activity in airway epithelial cells through Rho GTPase signaling pathways 1. Mechanistically, BPIFB1 is a critical component of the mucociliary clearance apparatus, colocalizing with MUC5B in secretory granules and integrating into the mucus protein network 2. Loss of BPIFB1 impairs mucociliary clearance and alters mucus biophysical properties without affecting ciliary function 2. In nasopharyngeal carcinoma, BPIFB1 suppresses metastasis by inhibiting vitronectin (VTN)-integrin signaling and epithelial-mesenchymal transition 3, while blocking VTN-mediated radioresistance through ATM-Chk2 and ATR-Chk1 pathway inhibition 4. BPIFB1 also inhibits vasculogenic mimicry via GLUT1-mediated metabolic reprogramming 5. Clinically, BPIFB1 dysregulation associates with multiple pulmonary diseases: elevated sputum BPIFB1 in COPD correlates with lung function decline 6, high lung BPIFB1 expression in idiopathic pulmonary fibrosis links to collagen synthesis and poor prognosis 7, and reduced BPIFB1 increases cystic fibrosis disease severity 1. In nasopharyngeal carcinoma, BPIFB1 downregulation associates with poor prognosis and metastatic disease 3. BPIFB1 autoantibodies appear in thymoma-associated autoimmune pneumonitis 8.