Nrp1

Neuropilin‑1 (Nrp1) is a cell surface receptor that belongs to the neuropilin family of transmembrane proteins. It is expressed in many tissues, including vascular endothelium, neurons, immune cells, and certain epithelial cells. The protein is a non‑covalently bound heterodimer of α and β subunits, with a large extracellular region that binds various ligands such as vascular endothelial growth factors (VEGF), class 3 semaphorins, and certain co‑factors. Nrp1 does not possess intrinsic kinase activity; instead, it recruits and modulates signaling through associated receptors (e.g., VEGFR2, plexins) to influence downstream pathways like Akt, MAPK, and Rho GTPases.

During embryonic development, Nrp1 is essential for vascular patterning, axon guidance, and nervous system organization. In angiogenesis, it functions as a co‑receptor for VEGF‑A165, enhancing VEGF binding to VEGFR2 and promoting endothelial cell migration and tubule formation. In the nervous system, Nrp1 mediates semaphorin‑3A induced growth cone collapse and axonal repulsion, contributing to the refinement of neural circuits. In the immune system, Nrp1 is expressed on regulatory T cells and has been implicated in their suppressive function, as well as on certain myeloid cells where it can modulate chemokine signaling.

Aberrant Nrp1 expression has been associated with various pathologies. Overexpression is observed in several cancers (breast, colorectal, glioblastoma), where it supports tumor angiogenesis, invasion, and metastasis. It also plays roles in chronic inflammatory diseases and neurodegenerative disorders. Consequently, Nrp1 is a target of therapeutic interest, with inhibitors and antibodies developed to disrupt its ligand interactions in oncology and vascular disease.