Epsins were originally isolated as adaptor proteins in the clatherin-mediated endocytosis of ubiquitylated cell surface receptors.[14,15] Using molecular, cellular, genetic, and mutant mouse models, we have identified that epsins modulate embryogenesis,[16] angiogenesis vasculature,[17] lymph angiogenesis,[18] tumor angiogenesis,[19,20] and cancer progression.[21] Mechanistic studies have demonstrated that epsins target the Notch[16] or ubiquitylated receptor VEGFR2,[17,19,20,22] VEGFR3 or Wnt signaling pathway,[21] and modulate angiogenesis or epithelial cell proliferation. This evidence concerns the gene KDR and neoplasm.