Neuropilin receptor (NRP)

Neuropilins (NRP1 and NRP2) are non-tyrosine kinase transmembrane glycoproteins that serve as essential co-receptors for a variety of extracellular ligands, most notably the Vascular Endothelial Growth Factor (VEGF) family and Class 3 Semaphorins [1, 2]. They play critical roles in physiological processes including embryonic development, axon guidance, and the regulation of angiogenesis and lymphangiogenesis [6, 7]. In pathological states, neuropilins are frequently overexpressed in numerous solid tumors, where they facilitate tumor progression, survival, and metastasis by enhancing pro-angiogenic signaling and promoting an immunosuppressive microenvironment [4, 13]. Beyond oncology, NRP1 has gained significant attention as a co-receptor for SARS-CoV-2 entry, facilitating viral infection [3, 17]. Therapeutic targeting of neuropilins, primarily through monoclonal antibodies like vesencumab or small molecule inhibitors, aims to disrupt their interaction with VEGF or other growth factors to overcome resistance to standard anti-angiogenic therapies [5, 9].

Other names

Neuropilin-1Neuropilin-2NRP1NRP2Vascular endothelial cell growth factor 165 receptorVEGF165RCD304BDCA4NP1NP2

Neuropilins function as co-receptors that lack intrinsic signaling activity but significantly enhance the signaling of other receptors, such as Vascular Endothelial Growth Factor Receptors (VEGFRs) and Plexins, by facilitating high-affinity ligand binding. Therapeutic agents typically target the b1 and b2 extracellular domains of NRP1 or NRP2 to competitively inhibit the binding of VEGF-A, VEGF-C, or Semaphorins, thereby suppressing downstream pathways like PI3K/Akt and MAPK/ERK that drive pathological angiogenesis, lymphangiogenesis, and tumor cell survival [1, 3, 5, 10].