RIG-I (RNA sensor RIG-I, encoded by DDX58) is a cytosolic pattern recognition receptor that detects viral nucleic acids and initiates innate immune responses 1. Upon sensing cytoplasmic viral RNAs—particularly 5'-triphosphorylated single-stranded RNAs and double-stranded RNAs with blunt-end 5' base pairing—RIG-I homooligomerizes into filamentous complexes on viral RNA substrates 2. This activation recruits mitochondrial antiviral signaling protein (MAVS), which engages kinases TBK1 and IKBKE to phosphorylate interferon regulatory factors IRF3 and IRF7, driving transcription of type I interferons and pro-inflammatory cytokines 3. RIG-I recognizes both positive and negative-strand RNA viruses including influenza, measles, dengue, and SARS-CoV-2, as well as certain DNA viruses like Epstein-Barr virus through dsRNA intermediates 2. RIG-I activity is tightly regulated by post-translational modifications and protein interactions; for example, TRIM25-mediated ubiquitination facilitates RIG-I oligomerization and pathway activation 4. Beyond antiviral immunity, RIG-I regulates cellular senescence by stabilizing CDKN1A mRNA, linking innate immunity to aging processes 5. Dysregulation causes disease: gain-of-function DDX58 variants cause lupus nephritis through RIG-I hyperactivation and excessive type I interferon signaling 6, while asparagine-mediated RIG-I degradation promotes immune evasion in cancer 7.