RNF115 (Ring Finger Protein 115) is an E3 ubiquitin ligase that catalyzes Lys-48 and Lys-63-linked polyubiquitination of diverse substrates, regulating multiple cellular pathways including autophagy, innate immunity, and cell proliferation 1. In antiviral immunity, RNF115 exhibits dual roles: it constitutively catalyzes K48-linked ubiquitination of MAVS leading to proteasomal degradation in uninfected cells, while catalyzing K63-linked ubiquitination of STING1 following viral infection to promote oligomerization and TBK1 recruitment 2. RNF115 promotes autophagosome-lysosome fusion by enhancing STX17 stability, facilitating autophagosome maturation 3. Additionally, RNF115 mediates Lys-11-linked ubiquitination of RAB1A and RAB13 to negatively regulate TLR-induced proinflammatory cytokine expression 4. Clinically, RNF115 plays pathogenic roles in multiple diseases. In autoimmunity, RNF115 promotes STING-mediated inflammation; RNF115 inhibition by disulfiram alleviates systemic inflammation in autoimmune models and reduces proinflammatory cytokines in systemic lupus erythematosus patients 5. In hepatocellular carcinoma, RNF115 suppresses ferroptosis by mediating K27 ubiquitination of DHODH, and YBX1-mediated m5C modification enhances RNF115 translation 6. In gastric and thyroid cancers, RNF115 promotes tumorigenesis and metastasis through enhanced autophagy and CDK10 degradation, respectively, correlating with poor prognosis 3, 7. RNF115 deletion protects against acute liver injury by promoting autophagy and attenuating inflammatory responses 8.