Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube. May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling. Potently inhibits endothelial cell proliferation and angiogenesis (PubMed:9459295). May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (By similarity). Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (PubMed:11257123). Forms homotrimers (PubMed:11257123). Recombinant non-collagenous domain 1 has stronger affinity to NID1, HSPG2 and laminin-1:NID1 complex and lower affinity to FBLN1 and FBLN2 than endostatin (By similarity). Monomeric (PubMed:11257123). Interacts with KDR/VEGFR2. Interacts with the ITGA5:ITGB1 complex. Interacts with NID1, HSPG2, laminin-1:NID1 complex, FBLN1 and FBLN2 (By similarity). Present in multiple organs with highest levels in liver, lung and kidney. Prolines at the third position of the tripeptide repeating unit (G-X-Y) of the triple-helical regions are hydroxylated. Circulating endostatins are found as sialoglycoprotein and asialoglycoprotein structures. Undergoes proteolytic processing by CTSL/cathepsin-L and elastase-like proteases to generate both non-collagenous domain 1 trimers and endostatin monomers (PubMed:10626789). In tissue extracts (brain, skeletal muscle, heart, kidney, testis and liver) predominantly bands of approximately 38 kDa are detected; recombinant non-collagenous domain 1 shows similar mobility. In vitro, several proteolytic cleavage sites in the non-collagenous domain 1 hinge region generating different endostatin-like peptides are reported (By similarity). There is an association between a polymorphism in position 1675 and prostate cancer. Heterozygous Asn-1675 individuals have a 2.5 times increased chance of developing prostate cancer as compared with homozygous Asp-1675 individuals. The disease is caused by variants affecting the gene represented in this entry. The disease may be caused by variants affecting the gene represented in this entry. Available under the name Endostar (Jiangsu Simcere Pharmaceutical) for the treatment of non-small-cell lung cancer. Produced by alternative promoter usage. Produced by alternative splicing of isoform 1. Produced by alternative promoter usage. Belongs to the multiplexin collagen family. Non-collagenous domain 1 seems to be the predominant tissue form from which endostatin is cleaved. However, the proteolytic cleavage site to generate non-collagenous domain 1 is not known. Soluble recombinant non-collagenous domain 1 amenable to biochemical studies has been used instead.