Based on limited published evidence, RNF208 is an E3 ubiquitin ligase localized to the nucleoplasm with ubiquitin-protein transferase activity. RNF208 catalyzes protein ubiquitination and autoubiquitination through its ring finger domain 1. The protein is S-nitrosylated by nitric oxide, which modulates its E3 ligase activity 2. Functionally, RNF208 targets soluble vimentin for polyubiquitin-mediated proteasomal degradation in triple-negative breast cancer cells, suppressing metastasis. RNF208 expression is induced by 17β-estradiol in an estrogen receptor alpha-dependent manner, and low expression correlates with poor clinical outcomes in TNBC 1.