Earlier studies have demonstrated that TWEAK induces NF-κB activation in EC, astrocytes, and neurons, and that either treatment with an Fn14-Fc decoy, or genetic deficiency of Fn14, abrogates cerebral ischemia-induced Iκκβ and p65 phosphorylation in the ischemic brain (24). The gene discussed is TNFSF12; the disease is brain ischemia.