Mast cell tryptase (TPSAB1) (TPSAB1)

Mast cell tryptase is the most abundant neutral serine protease stored in the secretory granules of mast cells and is released upon activation, often alongside related proteases like chymase (UniProt P15088, P23946). Tryptase is unique for its active form as a heparin-stabilized tetramer, which renders it resistant to most endogenous protease inhibitors (PubMed PMID: 31551145). It acts as a potent mediator of inflammation by cleaving and activating protease-activated receptor 2 (PAR-2), which induces the release of cytokines, promotes bronchoconstriction, and stimulates fibroblast proliferation (StatPearls NBK545201). In clinical settings, elevated tryptase levels serve as a diagnostic marker for mast cell activation and systemic mastocytosis, and are implicated in the pathophysiology of severe asthma and COPD (PubMed PMID: 29107048). Therapeutic development focuses on inhibiting tryptase's enzymatic activity or preventing tetramer formation using monoclonal antibodies like MTPS9579 or small molecules like BMS-986235 (Genentech Pipeline, BMS Pipeline). These interventions aim to mitigate the chronic inflammation and structural remodeling characteristic of mast cell-mediated disorders.

Other names

Tryptase alpha/beta-1Tryptase beta-1Tryptase-2Mast cell protease IITPSB2TPS1TPS2Mast cell chymase

Inhibition of the proteolytic activity of the tryptase tetramer, preventing the cleavage and activation of protease-activated receptor 2 (PAR-2) and other downstream inflammatory substrates.