TIMPs (tissue inhibitors of metalloproteinases) are endogenous inhibitors for MMPs (matrix metalloproteinases). The TIMPs consist of structurally and functionally distinct N- and C-terminal domains, each of which is stabilized by three disulfide bonds. The N-terminal domain binds to the active site of MMPs, inhibiting their proteolytic activities. The bidentate coordination of the zinc ion in the active site of an MMP by the N-terminal α-amino group and carbonyl group of the Cys residue in the cysteine switch is a key mechanism of inhibition with MMPs. The TIMP's C-terminal domain is known to bind hemopexin-like domain of pro-MMPs. TIMPs are broad-spectrum inhibitors of MMPs, but there are some differences in specificity among them. Mouse metalloproteinase inhibitor 1, TIMP-1, is more restricted in its inhibitory range than the other three TIMPs, having a relatively low affinity for the membrane-type MMPs, MMP-14, MMP-16, and MMP-24 as well as for MMP-19. Mouse TIMP-1 shares a 72% homology with its human counterpart. It is widely expressed in many mammalian tissues, notably in the reproductive organs. TIMP-1 is able to promote cell proliferation in a wide range of cell types and may also have an anti-apoptotic function. It has anti-angiogenic activity by preventing endothelial cell migration. CD63 has been identified as a receptor for TIMP-1. TIMP-1 binding to CD63 inhibits apoptosis and arrests cell growth. TIMP-1-null mice exhibit a number of alterations in processes associated with reproduction, steroidogenesis and impaired learning and memory. In addition, mice deficient in TIMP-1 exhibit enhanced MMP activity that would contribute to a reduction of atherosclerotic plaque size; neverthless, it promotes aneurysm formation.