Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine and contributes to a variety of inflammatory disease responses and programmed cell death. TNF-α is synthesized as a 26K type II membrane-bound precursor that is cleaved by a convertase to generate secreted 17K mature TNF-α. TNF-α converting enzyme (TACE) protein was recently purified and the human and mouse TACE cDNAs were cloned by several groups separately. TACE is a membrane-bond metalloprotease-disintegrin in the family of mammalian ADAM (for a disintegrin and metalloprotease). TACE also processes other cell surface proteins, including TNF receptor, TGF-α, L-selectin adhesion molecule, and alpha-cleavage of amyloid protein precursor (APP). TACE mRNA is expressed in a variety of human and murine tissues.