Endostatin is a 20 kDa protein fragment derived from the non-collagenous (NC1) domain of type XVIII collagen. It is an endogenous inhibitor of angiogenesis, specifically inhibiting endothelial cell proliferation and blood vessel formation. Initially identified as a factor produced by murine endothelioma cells, endostatin plays a crucial role in wound healing by inhibiting tumor growth and impairing vascular maturation. It is involved in endothelial cell adhesion and cytoskeletal organization. Endostatin may also contribute to downregulating angiogenesis in physiological processes such as wound healing and establishment of placental circulation. The anti-angiogenic activity of endostatin is attributed to its ability to inhibit endothelial cell proliferation and suppress VEGF and FGF-induced endothelial cell migration and adhesion. Many of these effects are thought to be mediated by interactions between endostatin and transglutaminase 2 expressed on endothelial cells, heparin, and integrins α5β1 and αVβ3.