SCGB3A1 (secretoglobin family 3A member 1) is a secreted cytokine-like protein with tumor suppressor properties that functions primarily in airway epithelium and other tissues. Expression is regulated by the transcription factor NF-Y and controlled by CpG methylation in its promoter region 1. SCGB3A1 defines a subset of secretory cells in conducting airways alongside related secretoglobins, with expression patterns altered in airway disease 2. Clinically, SCGB3A1 emerges as a significant biomarker for interstitial lung disease (ILA), with elevated blood levels associated with ILA presence (OR 2.43) and progression, showing predictive potential in machine-learning models 3. In lung adenocarcinoma, SCGB3A1 functions as a tumor suppressor; high expression correlates with improved prognosis and enhanced immune cell infiltration, with overexpression suppressing cell proliferation, migration, and invasion 4. SCGB3A1 expression is downregulated in specific COPD patient communities characterized by immune activation and small airway changes 5. In metastatic disease, SCGB3A1-expressing epithelial cells promote breast cancer liver metastasis through CD74-APP interactions with fibroblasts 6. Genetic variants in SCGB3A1 promoter and intronic regions appear protective against nasal polyposis 7, suggesting immunoregulatory functions across diverse airway pathologies.