We further demonstrate that (1) high levels of NRP2 expression positively correlate with PNET vascularity; (2) NRP2 modulates angiogenesis by promoting HUVEC migration via a VEGF/VEGFR2-independent pathway; (3) NRP2 induces F-actin polymerization by activating the actin-binding protein cofilin; (4) NRP2 upregulates cofilin activity by promoting SSH1 expression; and (5) inhibition of NRP2 suppresses PNET angiogenesis and tumor growth in vivo. This evidence concerns the gene CFL1 and neoplasm.