RNF157 is an E3 ubiquitin ligase with dual functions in neuronal protection and cellular proliferation control. In neurons, RNF157 ubiquitinates APBB1 (Fe65) for proteasomal degradation, preventing apoptosis and promoting neuronal survival 1. Independently of its ligase activity, RNF157 regulates dendrite growth and maintenance, potentially through a scaffold function 1. RNF157 acts downstream of PI3K and MAPK signaling pathways to regulate cell cycle progression 1. Beyond the nervous system, RNF157 functions as a tumor-promoting ubiquitin ligase in hepatocellular carcinoma, where it ubiquitinates RIG-I/DDX58 at lysine 48, promoting liver cancer cell proliferation and correlating with poor prognosis 2. In lens epithelial cells, RNF157 protects against oxidative stress-induced apoptosis by ubiquitinating and degrading p53, suggesting a role in age-related cataract prevention 3. RNF157 expression is dysregulated in multiple malignancies—upregulated in liver and ovarian cancers where it promotes tumor progression 2, 4—and identified as a prognostic marker in hepatocellular carcinoma 5. The lncRNA RNF157-AS1 regulates epithelial ovarian cancer cell behavior through autophagy suppression, influencing chemotherapy sensitivity 4. Additionally, SNPs in RNF157 regulatory regions associate with central obesity susceptibility 6.