NAPSA (napsin A aspartic peptidase) is an aspartic protease primarily expressed in lung alveolar cells and kidney podocytes 12. Its primary function involves processing of pneumocyte surfactant precursors and protein proteolysis within lysosomes and alveolar lamellar bodies 3. NAPSA has emerged as clinically significant in multiple disease contexts. In COVID-19 severity, NAPSA was identified as a putative causal gene through genome-wide association studies and multi-omics analysis, with variants at the 19q13.33 locus associated with respiratory failure in European populations 14. In clear cell renal cell carcinoma (ccRCC), reduced NAPSA expression in tumor tissues correlates with poor prognosis, and NAPSA downregulation enhances TGF-β1-induced epithelial-mesenchymal transition, suggesting a tumor suppressor role 2. NAPSA serves as a useful immunohistochemical marker for differential diagnosis, with NAPSA and ESR1 expression together showing 97.9% sensitivity and 72.2% specificity for distinguishing endometrial serous carcinoma from clear cell carcinoma 5. In lung adenocarcinoma, NAPSA was identified as part of a prognostic cell death signature associated with patient outcomes 6. These findings suggest NAPSA has potential utility as both a diagnostic biomarker and prognostic indicator across multiple malignancies.