Increased TPSAB1 copy number encoding α-tryptase is associated with generation of mature αβ-tryptase heterotetramers. Following mast cell activation and release of secretory granule contents, mature αβ-tryptases can contribute to mast cell degranulation in an autocrine manner through cleavage of the mechanoreceptor EMR2. αβ-Tryptases also selectively cleave and activate PAR2, potentially leading to increased acute vascular permeability and neuroinflammation. Mature β-tryptases have been shown to promote proliferation of connective tissue fibroblasts and airway smooth muscle cells which is associated with extracellular matrix remodeling and fibrosis. In the airways, mature β-tryptases have also been shown to promote smooth muscle tone, potentially in part by cleaving the bronchodilator VIP. *It is currently unknown whether αβ-tryptases have differential effects on connective tissue and airway phenotypes. EMR2, EGF-Like Module-Containing Mucin-Like Hormone Receptor-Like 2; PAR2, protease-activated receptor 2; VIP, vasoactive intestinal peptide; MRGPRX2, Mas-related G protein-coupled receptor-X2; FcεRI, high affinity IgE receptor.