[7][8][9] The metalloprotease domain is responsible for the enzyme's catalytic activity, cleaving membrane-bound proteins, including cytokines like TNF-alpha, to release their soluble forms.

ADAM17's activity is tightly regulated through multiple mechanisms, including the removal of its pro-domain and interactions with regulatory proteins such as TIMPs (tissue inhibitors of metalloproteinases).

[10] ADAM17 is understood to be involved in the processing of tumor necrosis factor alpha (TNF-α) at the surface of the cell, and from within the intracellular membranes of the trans-Golgi network.

ADAM17 was the first 'sheddase' to be identified, and is also understood to play a role in the release of a diverse variety of membrane-anchored cytokines, cell adhesion molecules, receptors, ligands, and enzymes.

Cloning of the TNF-α gene revealed it to encode a 26 kDa type II transmembrane pro-polypeptide that becomes inserted into the cell membrane during its maturation.

Research also suggests that the majority of mature, endogenous ADAM17 may be localized to a perinuclear compartment, with only a small amount of TACE being present on the cell surface.