Tumor-suppressive and immunomodulatory roles of BPIFB1/LPLUNC1: mechanistic insights from nasopharyngeal carcinoma and implications for multi-system diseases

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in Southeast Asia and Southern China and is closely associated with Epstein–Barr virus (EBV) infection. BPIFB1, also known as LPLUNC1, is an innate immune molecule abundantly expressed in the nasopharyngeal epithelium. It is markedly downregulated in NPC tissues, and its reduced expression is associated with poor patient prognosis. Accumulating evidence indicates that BPIFB1 is directly targeted and suppressed by EBV-encoded miR-BART4. Functionally, BPIFB1 acts as a multi-node tumor suppressor by regulating immune escape, metastatic invasion, glycolytic reprogramming, radioresistance, cell proliferation, and inflammation-associated signaling. In addition, BPIFB1 exhibits tissue-specific functional heterogeneity across multiple tumor types, including breast, lung, and gastric cancers. This review systematically summarizes the molecular structure of BPIFB1, the regulatory mechanisms underlying its aberrant expression, its multidimensional tumor-suppressive functions, and recent advances in BPIFB1-related research across multi-system diseases. We also discuss its translational potential as a biomarker and therapeutic target.