UGDH and UDP-GlcA are markedly downregulated in the livers of individuals with NAFLD or NASH, and UGDH absence from mouse hepatocytes promotes RIPK1 activation and hastens the development of NASH-associated liver damage and fibrosis by exaggerating hepatocyte apoptosis, which is suppressed by RIPK1 kinase-dead D138N knockin mutation. Here, UGDH is linked to metabolic dysfunction-associated steatohepatitis.