Zhao et al. (2018) and Zhang Y. et al. (2019) demonstrated that deficiency of USP4 in mouse livers disrupts signaling through the TAK1/JNK-mediated insulin receptor substrate/protein kinase B/glycogen synthase kinase 3β (IRS-AKT-GSK3) axis, giving rise to non-alcoholic fatty liver disease (NAFLD). The gene discussed is IARS1; the disease is metabolic dysfunction-associated steatotic liver disease.