The tumor necrosis factor-α (TNF-α) signaling pathway depends on TNF-alpha binding to its cell surface receptor, which activates the receptor and attracts adaptor proteins like TRAF and TRADD to create Complex I (9). This complex triggers downstream signaling pathways that control inflammatory responses and cell viability, such as MAP kinase pathways and NF-kB activation . Likewise, membrane-bound TNF-alpha can be broken by enzymes such as TNFalpha converting enzyme (TACE or ADAM17), releasing soluble TNF-alpha into the extracellular space . TACE is a popular therapeutic target for inflammation, such as rheumatoid arthritis, psoriasis, and various cancers. TNF-alpha amplifies inflammatory cascades and modulates immunological responses by acting as a paracrine signal. TNF-alpha signaling, which is mediated via receptor activation and enzyme-mediated cleavage pathways, is essential for immunity and inflammation The structure and cleavage mechanism proposed in this research will help us understand the atomistic details of this process and will aid in designing novel therapeutics against the TACE enzyme.