The E3 ubiquitin-protein ligase synoviolin is also known as human HRD1. The original HRD1 (HMG-CoA reductase degradation) gene was identified as a mutant gene in yeast deficient for the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR). Homology between the human and yeast gene is limited to the N-terminal domain of the proteins, and human HRD1/Synoviolin does not appear to be involved in the degradation of mammalian HMGR. Synoviolin is involved in endoplasmic reticulum (ER)-associated degradation. It removes unfolded proteins, accumulated during ER stress, by retrograde transport to the cytosol from the ER. This protein also uses the ubiquitin-proteasome system for additional degradation of unfolded proteins.