ERN1 and hepatocellular carcinoma: HRD1 upregulation is associated with the propensity of hepatocellular carcinoma (HCC) to metastasize.476 The upregulation of the SEL1L-HRD1 complex, which is positively correlated with survival time in liver cancer patients, promotes ERAD of misfolded WNT5A.477 IRE1α contributes to HRD1 upregulation in HCC cells, leading to CD155 degradation.478 HRD1 has also been implicated in mitochondrial biogenesis.