Neuropilin-1 (NRP1) is a non-tyrosine kinase receptor for vascular endothelial growth factor (VEGF) and a co-receptor for VEGF receptor 2 (VEGFR2) signalling in the endothelium. There is increasing evidence that NRP-1 plays a pivotal role in endothelial migration and angiogenesis, but the mechanisms involved are unclear. Recently, we have shown that NRP-1 is required for VEGF-mediated phosphorylation of the adaptor protein, p130Cas, a critical signalling hub in the regulation of cell motility, and this novel NRP-1-p130Cas pathway is important for endothelial cell migration (Evans et al 2011). Here we show that knockdown of either p130Cas or NRP-1 inhibits the VEGF-induced decrease in endothelial adhesion to fibronectin. Furthermore, NRP-1 and p130Cas are required for VEGF-induced focal adhesion kinase (FAK) phosphorylation, and NRP-1/p130Cas knockdown reduces immunofluorescent staining of focal adhesions by an anti-paxillin antibody. These findings indicate a key role for a NRP-1/p130Cas pathway in VEGF-induced focal adhesion turnover. NRP-1 modulation of focal adhesion turnover is likely to be an important mechanism mediating its role in endothelial migration and angiogenesis.