NRP2 (neuropilin 2) is a multifunctional cell surface receptor with primary roles in viral entry, axon guidance, and immune regulation. As a primary function, NRP2 serves as a cellular receptor for human cytomegalovirus (HCMV) pentamer-dependent entry into epithelial and endothelial cells 1. Mechanistically, NRP2 functions as a semaphorin receptor, particularly binding semaphorin 3G (Sema3G) and semaphorin 3C (SEMA3C) to coordinate vascular remodeling and endothelial-mesenchymal transition through PlexinD1 co-receptors 23. In the nervous system, NRP2 participates in axon guidance and nerve development, with NRP2+ fibroblasts identified in the neural microenvironment 4. Disease relevance includes ischemic retinopathies, where Sema3G-NRP2 signaling promotes healthy vascular remodeling and suppresses pathological angiogenesis 2. In diabetic kidney disease, mesangial-derived SEMA3C-NRP2 signaling drives glomerular endothelial dysfunction 3. NRP2 expression is transcriptionally regulated by CENPA in hepatocellular carcinoma, promoting proliferation 5. Clinically, NRP2 represents a therapeutic target: HARSWHEP, a histidyl-tRNA synthetase splice variant, binds NRP2 on myeloid cells to suppress inflammatory pathways and reduce fibrosis in interstitial lung disease 6. NRP2 also contributes to cardiac development through IGF2/IGF1R cross-talk signaling 7.