RNF19B is an E3 ubiquitin ligase that catalyzes ubiquitin transfer to targeted substrates such as UCKL1, working in partnership with E2 conjugating enzymes UBE2L3 and UBE2L6. The protein is involved in cytolytic activity of natural killer and cytotoxic T cells, and protects against staurosporin-induced cell death. Recent evidence suggests RNF19B plays broader roles in immune regulation and cancer biology. In hepatocellular carcinoma (HCC) patients, elevated RNF19B expression is associated with unfavorable survival outcomes and facilitates macrophage polarization toward the immunosuppressive M2 phenotype, with positive correlation to PD-1 and CTLA-4 1. In prostate cancer, aging-related hypermethylation of the transcription factor ZNF573 downregulates RNF19B expression, which in turn reduces ubiquitination of PIK3CA and promotes cancer cell proliferation and invasion 2. Additionally, RNF19B contributes to immune dysregulation in spinal muscular atrophy, with elevated NF-κB-mediated inflammatory signaling emerging post-gene therapy 3. RNF19B also participates in M1 macrophage polarization, with circulating RNF19B transcripts upregulated during pro-inflammatory macrophage activation 4. These findings position RNF19B as a multi-functional immune regulator with potential clinical significance in cancer immunotherapy and inflammatory disease contexts.