RTP4 (receptor transporter protein 4) functions as a dual-role Golgi chaperone with distinct roles in receptor trafficking and antiviral immunity. As a chaperone protein, RTP4 facilitates cell surface expression of G-protein coupled receptors, including the bitter taste receptor TAS2R16 1. However, RTP4's primary characterized function involves potent antiviral activity. As an interferon-stimulated gene (ISG), RTP4 restricts replication of multiple RNA viruses including influenza A, West Nile virus, yellow fever virus, and flaviviruses 23. For influenza A specifically, RTP4 directly targets the viral NS1 protein in an RNA-dependent manner, sequestering it from the TRIM25-RIG-I complex and restoring antiviral signaling through IRF3 activation 4. However, RTP4 demonstrates context-dependent immunoregulation: while enhancing antiviral responses in most tissues, it negatively regulates TBK1 signaling in the brain, suppressing type I interferon responses and exacerbating cerebral malaria pathology 5. Clinically, RTP4 genetic variants associate with fatigue severity in primary Sjögren's syndrome patients, correlating with type I interferon activity 6. These findings reveal RTP4 as a critical but pleiotropic regulator of both receptor biology and antiviral immunity with tissue-specific functions.