RNF19B is an E3 ubiquitin ligase that accepts ubiquitin from E2 conjugating enzymes (UBE2L3 and UBE2L6) and transfers it to substrate proteins such as UCKL1 1. The protein functions as part of the ubiquitin-proteasome system, where it catalyzes ubiquitination of small molecules and proteins, leading to their degradation or functional modification 2. RNF19B plays roles in immune regulation, contributing to cytolytic activity of natural killer cells and cytotoxic T-cells 3, and protects against staurosporin-induced apoptosis 4. Clinically, RNF19B has emerged as a significant prognostic marker in hepatocellular carcinoma, where elevated expression correlates with poor survival outcomes and M2 macrophage polarization 5. In prostate cancer, RNF19B mediates PIK3CA ubiquitination downstream of the transcription factor ZNF573, influencing cancer progression 6. Additionally, RNF19B functions as a component in natural killer cell-related prognostic signatures for clear-cell renal cell carcinoma 7. Recent evidence indicates RNF19B serves as a key transcriptomic mediator of immune dysregulation and NF-κB-related inflammation in spinal muscular atrophy, particularly post-gene therapy 8. The protein is also involved in macrophage polarization dynamics, with circRNF19B expression distinguishing M1 from M2 phenotypes 9.