Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of matrix metalloproteinases (MMPs). This family of inhibitors is consisted of four members, TIMP-1, -2, -3 , and -4.? Their structures are subdivided into an N-terminal and a C-terminal subdomain. A larger N-terminal domain carries the MMP inhibitory activity and a smaller C-terminal domain mediates other non-inhibitory interactions. Human TIMP-4 is the largest of the currently identified TIMPs. It binds to the hemopexin domatin of pro-MMP-2 as TIMP-2 does and inhibits MT1-MMP with high potency. However, TIMP-4 is unable to promote the activation of pro-MMP-2. Expression of TIMP-4 has been observed in heart, kidney, pancreas, colon, testes, brain and adipose tissue. Elevated levels of TIMP-4 have been found in breast, ovary, cervical, prostate, brain, colon, endometrium, and papillary renal tumors. It has been observed that the TIMP-4 expression has been down regulated epigenetically in failing heart.