In line with human evidence, deletion of both TRAF2 and RIP1 in liver parenchymal cells (LPC) leads to spontaneous development of hepatocellular carcinoma, which results from extensive hepatocyte apoptosis due to hyperactivation of caspase-8 but impaired NF-κB activation induced by TNFα (Table 2) (43). The gene discussed is CASP8; the disease is hepatocellular carcinoma.