Tumor Necrosis Factor Ligand Superfamily Member 15 (TNFSF15) is a new member of the tumor necrosis factor family. TNFSF15 is predominantly an endothelial cell-specific gene, and recombinant TNFSF15 is a potent inhibitor of endothelial cell proliferation, angiogenesis and tumor growth. TNFSF15 exerts two activities on endothelial cells: early G1 arrest of G0/G1-cells responding to growth stimuli and programmed cell death of proliferating cells. These activities are highly specific to endothelial cells. TNFSF15 is also able to regulate the expression of several important genes involved in angiogenesis. These findings are consistent with the view that TNFSF15 functions as an autocrine cytokine to inhibit angiogenesis and stabilize the vasculature.