Tissue inhibitor of metalloproteinases 4 (TIMP4)

Tissue inhibitor of metalloproteinases 4 (TIMP4) is a member of the TIMP family of metalloproteinase inhibitors, functioning primarily in the regulation of extracellular matrix (ECM) turnover by inhibiting various matrix metalloproteinases (MMPs) and some ADAM/ADAMTS proteases[1]. It is a 195-amino acid, non-glycosylated polypeptide, and the largest of the four human TIMPs[1]. TIMP4 directly inhibits MMPs such as MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, and MMP-9, among others, with high specificity, as well as some ADAM and ADAMTS proteases, though with lower efficiency compared to some other TIMPs[1]. Beyond its protease-inhibiting function, TIMP4 can influence cell survival by modulating apoptosis pathways—downregulating anti-apoptotic proteins such as Bcl-2 and cIAPs, increasing the sensitivity of cancer cells to cell death signals, and altering caspase activation[2]. It plays major roles in normal physiology and disease, including regulating platelet function, modulating tumor cell survival and metastasis, and impacting vascular pathology such as atherosclerosis by controlling ECM and smooth muscle cell proliferation[1][2][3]. Expression levels and functional activity of TIMP4 are altered in cancer, cardiovascular, and inflammatory diseases, making it a key biomolecule of interest for both basic research and potential therapeutic targeting.

Other names

Metalloproteinase inhibitor 4TIMP-4Tissue inhibitor of metalloproteinase 4Tissue inhibitor of metalloproteinases 4

Inhibition of matrix metalloproteinase activity (prevents ECM breakdown); Modulation of proteolytic activity of ADAM and ADAMTS family proteases