In the liver of patients with nonalcoholic steatohepatitis (NASH), free fatty acid upregulates the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) death receptor 2 (TRAIL-R2) expression in hepatocytes through activating JNK signaling, and then turns hepatocytes from TRAIL cytotoxicity resistant to sensitivity. Here, TNFRSF10B is linked to metabolic dysfunction-associated steatohepatitis.