The dimerization and subsequent autophosphorylation of ASK1 are essential for its activation.322,323 CFLAR directly targets ASK1 and interrupts its N-terminus-mediated dimerization, thereby blocking signaling involving ASK1 and JNK1.324 Tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) is a pivotal endogenous suppressor of ASK1 hyperactivation in the pathogenesis of NASH. This evidence concerns the gene MAPK8 and metabolic dysfunction-associated steatohepatitis.