PRTN3 encodes proteinase 3, a neutrophil-derived serine protease with diverse functions in immune regulation, tissue remodeling, and disease pathogenesis. The protein degrades extracellular matrix components including elastin and collagen, and enhances endothelial barrier function by cleaving receptor F2RL1/PAR-2 during neutrophil transendothelial migration 1. PRTN3 plays a critical role in immune suppression by promoting M2 polarization of tumor-associated macrophages through an AKT-FOXO1-IL33 signaling pathway, which enhances regulatory T cell-mediated immunosuppression in lung adenocarcinoma 2. Additionally, PRTN3 inhibits myeloid differentiation by negatively regulating STAT3 through promoting its ubiquitination and degradation while reducing phosphorylation and nuclear translocation 3. Clinically, PRTN3 serves as a biomarker for multiple cancers, with elevated expression associated with poor prognosis in hepatocellular carcinoma following radiofrequency ablation 4 and serving as an early diagnostic marker for gastric cancer 5 and lung adenocarcinoma through autoantibody detection 6. A genetic variant upstream of PRTN3 correlates with increased autoantigen levels and relapse risk in PR3-ANCA vasculitis 7. The gene is located on chromosome 19 in humans and chromosome 19 in mice 8.