RNF144A is an RBR-family E3 ubiquitin ligase that catalyzes ubiquitin transfer to target proteins for proteasomal degradation 1. It accepts ubiquitin from E2 enzymes UBE2L3 and UBE2L6 and directly transfers ubiquitin to substrates 1. RNF144A functions across multiple cellular processes. It mediates PRKDC ubiquitination and degradation during DNA damage 2. It positively regulates innate immunity by promoting STING1 ubiquitination and its ER-to-Golgi translocation during viral or cytosolic DNA sensing 3. RNF144A enhances EGF-dependent cell proliferation through EGFR ubiquitination-mediated signaling prolongation 4 and increases ERK activity by promoting VRK3 polyubiquitination and degradation 5. Additionally, RNF144A inhibits autophagy by promoting K48-linked ubiquitination of BECN1 at K117 and K427, leading to its proteasomal degradation 6. Clinically, RNF144A exhibits tumor-suppressive functions. RNF144A deficiency is associated with increased bladder tumorigenesis upon carcinogen exposure, correlating with elevated PD-L1, DNA-PKcs, and BMI1 expression 7. Conversely, genetic variants in RNF144A are associated with aortic stenosis risk independent of coronary artery disease 8. The lncRNA RNF144A-AS1, transcribed from the RNF144A locus, promotes gastric cancer and hepatocellular carcinoma progression through miRNA-sequestering mechanisms [PMID:34583752; 99].