FETUB (fetuin B) is a glycoprotein protease inhibitor with diverse physiological roles. Traditionally, FETUB is required for proper egg fertilization by inhibiting the metalloprotease ASTL, thereby preventing premature zona pellucida hardening before sperm-egg fusion 1. However, emerging evidence reveals pathological functions in respiratory and metabolic diseases. In asthma, epithelial-derived FETUB exacerbates airway inflammation by inhibiting neprilysin (NEP) activity, leading to accumulation of neuropeptides CGRP and SP; IL-13 induces epithelial FETUB expression, and lung-specific FETUB knockdown improves airway hyperresponsiveness 2. In diabetic retinopathy, FETUB interacts with insulin receptor-β to suppress insulin signaling via the PI3K/Akt pathway in retinal cells 3. FETUB elevation correlates with COPD severity, predicting acute exacerbation and lung function decline 4. Additionally, FETUB links vitamin D deficiency to pediatric obesity through direct VD/VDR-mediated regulation 5. FETUB has emerged as a biomarker in TB diagnosis, with a 6-protein panel including FETUB distinguishing pulmonary TB patients from healthy controls and other respiratory infections 6. In asthma specifically, FETUB represents a hub gene in modules correlating with elevated IgE in youth 7, suggesting neuroimmune coregulation. These findings indicate FETUB functions as both a reproductive protease inhibitor and a pathogenic mediator in inflammatory and metabolic disorders.