Intervention of lymphoedema may be achieved through TNFSF15-enhancement of the VEGFR3-mediated signaling pathways.93 Additionally, it was reported that VEGFR3 has an inhibitory activity on VEGFR2 expression and VEGF/VEGFR2 signaling in vascular endothelial cells, thereby preventing the development of excessive vascular permeability.45 Because low levels of VEGFR3 are also present in vascular endothelial cells in a stable vasculature,94,95 the upregulation of VEGFR3 gene expression by TNFSF15 likely contributes to the maintenance of vascular stability (Fig. 3). Here, FLT4 is linked to lymphedema.