SERPINB6 is an intracellular serine protease inhibitor with multifaceted roles in cellular protection and disease pathogenesis. Primarily, it inhibits serine proteases including cathepsin G, kallikrein-8, and thrombin 1, and is abundantly expressed in mast cells where it regulates beta-tryptase activity 2. In the inner ear, SERPINB6 protects against lysosomal content leakage during stress, and loss of this protection results in sensorineural hearing loss (associated with autosomal recessive deafness 91) 2. SERPINB6 localizes to cytoplasm and extracellular regions, functioning as a cellular defense mechanism in leukocytes, epithelial cells, and endothelial cells 2. Mechanistically, SERPINB6 regulates reactive oxygen species levels in epithelial tissue 3 and controls intracellular protease activity through inhibitory complex formation 2. In glioma, SERPINB6 promotes epithelial-mesenchymal transition via PI3K/AKT/mTOR pathway activation, enhancing cellular invasion 4. Conversely, dutomycin targets SERPINB6 to activate intracellular serine proteases, inducing autophagy and apoptosis in tumor cells 5. Clinically, SERPINB6 has emerged as a biomarker with disease relevance across neurological and neoplastic conditions. Mendelian randomization studies identified SERPINB6 as a feature gene associated with Alzheimer's disease progression 6 and type 1 diabetes susceptibility 7. The amygdala neuropsin/SERPINB6 pathway regulates anxiety-related gastric hypersensitivity in functional dyspepsia 8.