NEURL3 (neuralized E3 ubiquitin protein ligase 3) is an E3 ubiquitin ligase that functions as a multi-faceted innate immune regulator and tumor suppressor. Structurally, NEURL3 contains a RING domain conferring E3 ligase activity 1 and utilizes ubiquitin-conjugating enzymes to catalyze polyubiquitination of diverse substrates. Primary functions include: (1) antiviral immunity—NEURL3 promotes K63-linked ubiquitination of IRF7 at lysine 375, enhancing interferon-stimulated gene transcription and type I interferon production 2; (2) hepatitis C virus suppression via direct binding to viral E1 glycoprotein, disrupting E1/E2 heterodimerization required for virion assembly 3; and (3) amplification of TLR-mediated signaling through K48-linked polyubiquitination of phosphatase DUSP1/MKP1, promoting sustained MAPK activation 4. Clinically, NEURL3 expression is induced during inflammation and viral infection through pattern recognition receptor signaling 35. In nasopharyngeal carcinoma, NEURL3 promoter hypermethylation correlates with reduced expression, poor prognosis, and metastasis; restoration suppresses epithelial-mesenchymal transition via vimentin degradation 6. NEURL3 knockdown also inhibits proliferation and motility in esophageal squamous cell carcinoma 7, suggesting tumor suppressive roles.