Mechanistically, FBXW5 increases Lys63-linked ASK1 ubiquitination, aggravating ASK1-JNK/p38MAPK signaling, upregulation of lipid metabolism genes (CD36, PPARα, MCAD, and PDK4), and increase in proinflammatory factors (IL-6, IL-1b, and TNF), which aggravated NASH inflammation and lipid accumulation (44). Here, MAPK8 is linked to metabolic dysfunction-associated steatohepatitis.