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The evolutionary conservation of the catalytically inactive α-tryptase gene has remained a mystery. In this issue of JEM , Le et al. (2019. J. Exp. Med. https://doi.org/10.1084/jem.20190701) unveil the existence of a novel but natural tryptase, heteromeric α/β-tryptase, a critical mediator of α-tryptase-associated diseases.

When alpha meets beta, mast cells get hyper