PGA4 (pepsinogen A4) encodes a gastric pepsinogen that functions as the inactive precursor to pepsin, an aspartic-type endopeptidase with broad substrate specificity 1. PGA4 is normally expressed in human stomach tissue but not in healthy lung tissue, making it a specific biomarker for aspiration when detected in airways 1. In lung transplant recipients, airway PGA4 levels identify patients with microaspiration and predict chr11 lung allograft dysfunction (CLAD), with elevated levels associated with increased CLAD risk in two independent cohorts 1. Antireflux surgery significantly reduces airway PGA4 levels, supporting its utility as a therapeutic monitoring biomarker 1. The PGA4 gene exhibits polymorphic variation as part of pepsinogen haplotypes containing different combinations of PGA3, PGA4, and PGA5 genes, likely resulting from gene duplication events during molecular evolution 2. In pan-cancer analysis, PGA4 expression is generally decreased in cancer tissues compared to normal tissues and shows prognostic significance, being associated with improved survival specifically in kidney renal clear cell carcinoma 3. PGA4's clinical significance lies primarily in its role as a specific aspiration biomarker for risk stratification and surgical decision-making in lung transplant recipients.