The disassembly of Fn14 from E3 ligase SCFFbxw7 is sufficient to dismantle the K48-linked polyubiquitination of Fn14 and stabilizes it, while pharmacological deactivation of Fn14 effectively prevents the LPS-stimulated tubular damage in vitro and provides kidney protection against septic AKI in mice 12. The gene discussed is TNFRSF12A; the disease is acute kidney injury.