TIMP2 functions to activate and inhibit matrix metalloproteinases, which are involved in degrading the extracellular matrix. TIMP2 can directly suppress endothelial cell proliferation, and in the brain it has additional functions in cognition and in age-related hippocampal function. It plays a pivotal role in maintaining tissue homeostasis by blocking protease activity in tissues undergoing remodeling of the extracellular matrix and by suppressing quiescent tissue proliferation in response to angiogenic factors. In gastric cancer, higher TIMP2 expression is correlated with poorer survival and may serve as a useful diagnostic biomarker for the disease. In immunohistochemistry of normal tissue, TIMP2 has extracellular and cytoplasmic positivity in all tissues throughout the body. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Gastric Cancer. Sci Rep 8, 9629 (2018) doi:10.1038/s41598-018-27897-x; Nature. 544 (7651): 488–492, PMID: 28424512;