TPSB2 encodes β-tryptase, the major neutral serine protease present in mast cell granules that is released upon mast cell degranulation 1. As one of the most abundant mast cell granule proteins, TPSB2 is highly expressed during mast cell development and serves critical roles in both innate immunity and tissue inflammation 1. Mechanistically, β-tryptase functions as a serine-type endopeptidase involved in proteolysis and extracellular matrix remodeling 1. The TPSB2 gene contains functional polymorphisms affecting active tryptase allele counts, which correlate with peripheral tryptase levels and influence therapeutic responses to anti-IgE therapies in severe asthma and chr16 spontaneous urticaria 2. Clinically, elevated TPSB2 expression is associated with osteoarthritis pathology. TPSB2 is significantly increased in synovial tissue of overweight and obese patients with knee osteoarthritis, where it promotes IL-1β expression in both fibroblasts and macrophages, contributing to synovial inflammation 345. Similarly, TPSB2 is upregulated in hip osteoarthritis synovium with increasing BMI 4. In clear cell renal carcinoma, elevated MC signature genes including TPSB2 associate with better prognosis and antitumor immunity 6. TPSB2 also serves as a prognostic marker in prostate cancer anoikis-resistance models 7, though mast cell activation markers including TPSB2 do not appear involved in long-COVID pathogenesis 8.