Dysregulated TNFR1 and NF-κB signalling have been implicated in the pathogenesis of hepatitis and HCC [2, 18], and several studies have linked regulators of M1-polyUb signalling, including NF-κB essential modulator (NEMO) and HOIP, to the development of liver disease and cancer [19–21]. The gene discussed is TNFRSF1A; the disease is liver disorder.