NTN4 (netrin 4) is a secreted glycoprotein primarily recognized for axon guidance and neurite elongation 1, with critical roles extending beyond neural development to vascular and kidney development 2. The protein functions as a ligand for receptors including Neogenin and UNC5B 2, mediating cell migration and basement membrane assembly 3. Mechanistically, NTN4 promotes neurite outgrowth in human sensory neurons 1 while simultaneously regulating inflammatory responses. It stimulates production of pro-inflammatory cytokines (IL-6, IL-8) and chemokines (CXCL1, CXCL6, CXCL8) in fibroblastic cells 1, and upregulates IL-17 and TNF-α signaling pathways 4. NTN4 controls angiogenesis and endothelial homeostasis 2, with expression negatively regulated by the oncogenic miR-17-92 cluster 5. Clinically, elevated synovial and infrapatellar NTN4 expression correlates with pain severity and advanced knee osteoarthritis 14. Reduced hepatic NTN4 levels associate with hepatocellular carcinoma progression, particularly portal vein invasion 2. Lower breast cancer tissue NTN4 expression predicts poorer survival 3, and genetic variants in NTN4 (rs17356907) influence breast cancer susceptibility through interaction with miR-17-92 polymorphisms 6. Additionally, NTN4 variants associate with Tourette syndrome 7 and Meniere's disease 8, implicating axonal guidance dysfunction in neurological disorders.