TPL-2/ERK1/2 signaling is required for cytokine and chemokine production, with TPL-2-deficient (Map3k8–/–) mice being protected in models of endotoxic shock, experimental autoimmune encephalomyelitis (EAE) [9], pancreatitis, liver fibrosis and thrombocytopenia [10–15]. The gene discussed is MAP3K8; the disease is experimental autoimmune encephalomyelitis.