Mediates a variety of processes including matrix regulation and turnover, inflammation, and angiogenesis, through reversible inhibition of zinc protease superfamily enzymes, primarily matrix metalloproteinases (MMPs). Regulates extracellular matrix (ECM) remodeling through inhibition of matrix metalloproteinases (MMP) including MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15. Additionally, modulates the processing of amyloid precursor protein (APP) and apolipoprotein E receptor ApoER2 by inhibiting two alpha- secretases ADAM10 and ADAM17 (PubMed:17913923). Functions as a tumor suppressor and a potent inhibitor of angiogenesis. Exerts its anti- angiogenic effect by directly interacting with vascular endothelial growth factor (VEGF) receptor-2/KDR, preventing its binding to the VEGFA ligand (PubMed:12652295). Selectively induces apoptosis in angiogenic endothelial cells through a caspase-independent cell death pathway (PubMed:25558000). Mechanistically, inhibits matrix-induced focal adhesion kinase PTK2 tyrosine phosphorylation and association with paxillin/PXN and disrupts the incorporation of ITGB3, PTK2 and PXN into focal adhesion contacts on the matrix (PubMed:25558000). {ECO:0000250|UniProtKB:P39876, ECO:0000269|PubMed:12652295, ECO:0000269|PubMed:17913923, ECO:0000269|PubMed:25558000}. This is the function of TIMP3 (TIMP metallopeptidase inhibitor 3, Ensembl gene identifier ENSG00000100234).