Surprisingly, unlike CYLD-deficient livers, TNFR1 signalling is dispensable for steatohepatitis and pre-malignant tumour development in Otulin∆hep livers, clearly indicating that the liver diseases caused by deficiency in the two main M1-polyUb-regulating DUBs, OTULIN, and CYLD, have distinct pathogeneses. Here, OTULIN is linked to liver disorder.