ADAM17: A Major “Sheddase” in Human Disease

ADAM17 belongs to the “A Disintegrin and Metalloprotease Domain (ADAM)” family of cell membrane-anchored enzymes. Known as “sheddases”, ADAM17 and its catalytically active relatives appear to cleave a long list of membrane-bound substrates (at least 80, including TNF-α, IL6R, TNFR1, ACE2 and EpCAM) resulting in profound effects on signaling triggered by the liberated ectodomains and/or the subsequently processed intracellular domains (1). Despite its essential roles in development and homeostasis, ADAM17 has generated particular interest for its functions in inflammation, fibrosis, autoimmune disease, and tumor cell immune evasion. It also acts in cancer progression, invasion, neovascularization, and drug resistance. Broadly expressed in both somatic and immune cells, ADAM17 is a key player in the severe inflammatory process associated with some cases of COVID-19 (2).

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