HMGB1 and hepatocellular carcinoma: JNK1-mediated cell death also results in the release of high mobility group box 1 (HMGB1) protein, which in turn activates TLR4 in neighboring hepatocytes to enhance liver inflammation and injury [135] These dysfunctions of the ER and mitochondria induced by FC accumulation contribute to liver injury and HCC development through compensatory proliferation.