Doa10, a membrane-embedded ubiquitin ligase, facilitates the removal of membrane proteins from the endoplasmic reticulum and cooperates with the Cdc48 ATPase in this process.

UBIAD1 mediates a unique geranylgeranyl pyrophosphate-sensing mechanism that when disrupted, inhibits degradation of HMG CoA reductase and triggers overproduction of corneal cholesterol that characterizes the eye disease Schnyder Corneal Dystrophy.

Embryonic lethality associated with deficiency of UBIAD1, which synthesizes a vitamin K₂ subtype, results from aberrant ER-associated degradation of the cholesterol biosynthetic enzyme HMG CoA reductase.

A deubiquitinase antagonizes the activity of an associated E3 ligase to prevent uncontrolled ubiquitination of a degradation machinery protein and thus maintain its functionality in protein quality control at the endoplasmic reticulum.

Endoplasmic reticulum-associated degradation (ERAD) is a critical protein quality control checkpoint for thymocyte β-slection.

The fate of glycoproteins in the endoplasmic reticulum whether they are directed toward folding or targeted to degradation depends on a tug of war between UGGT1 and EDEM family proteins.

The inhibition of sterol-accelerated degradation of HMG CoA reductase by the vitamin K2 synthetic enzyme UBIAD1 may contribute to the accumulation of cholesterol that is associated with Schnyder corneal dystrophy.

Type 1 polyisoprenoid diphosphate phosphatase (PDP1) contributes to interconversion of isoprenols and isoprenylpyrophosphates, balancing the sterol and nonsterol branches of the mevalonate pathway by regulating ERAD of HMG CoA reductase and ER-to-Golgi transport of UBIAD1.

CRISPR/Cas9 genome-wide screens using sterol-sensitive endogenous HMG-CoA reductase (HMGCR) reporter identify the sterol-responsive RNF145 and gp78 as independently responsible for sterol-accelerated degradation of HMGCR, the rate-limiting enzyme of cholesterol biosynthesis.

The mechanism identified here that mediates olanzapine-induced b-cell dysfunction should be considered, along with weight gain, in mitigating adverse side effects when patients with schizophrenia are prescribed olanzapine.