NRP1 (neuropilin-1) is a transmembrane co-receptor with diverse roles in pathophysiology. Structurally, NRP1 contains an extracellular b domain that mediates ligand binding and facilitates receptor interactions at the plasma membrane and signaling endosomes 1. Primary functions include modulating growth factor and cytokine signaling across multiple pathways. NRP1 serves as a co-receptor for nerve growth factor (NGF), enhancing NGF/TrkA pain signaling through interaction with the NGF C-terminal R/KXXR/K motif and chaperoning TrkA to the cell surface 1. NRP1 also co-localizes with TGF-β and TNF-α receptors, facilitating their signaling in distinct cell types 2. Additionally, NRP1 functions as a host factor for viral entry; it binds SARS-CoV-2 spike protein S1 CendR motif 3 and hepatitis B virus preS1 domain, promoting viral internalization 4. In cancer immunology, NRP1 expression on regulatory T cells (Tregs) is essential for intratumoral Treg stability, and high NRP1+ Treg levels correlate with poor prognosis in melanoma and head and neck cancers 5. Tumor-expressed NRP1 sustains macropinocytosis through O-GlcNAcylation, suppressing MHC class II expression and promoting immunosuppression; DHODH-NRP1 axis inhibition overcomes anti-PD1 resistance 6. In intestinal immunity, NRP1 promotes IL-17 production by ILC3s, driving colitis progression in inflammatory bowel disease 7. NRP1 upregulation in renal distal tubules exacerbates fibrosis through TNF-α signaling and collagen secretion 2. NRP1 also mediates NSCLC radioresistance via YAP/TEAD4-driven transcription 8.