Human TEB4, an E3 ligase resident in the ER membrane, degrades squalene monooxygenase (SM) to inhibit cholesterol synthesis.392 Glycoprotein 78 (gp78) can enhance the ubiquitinated degradation of HMGCR,393 insulin-induced gene 1 protein (INSIG1)394 and ApoB-100.395 Hepatic gp78 deficiency alleviates hyperlipidemia and insulin resistance through reducing lipid biosynthesis. The gene discussed is AMFR; the disease is Insulin resistance.