Insig facilitates the degradation of HMG-CoA reductase. In the presence of sterols, a subclass of Insig associated with ubiquitinating enzymes binds HMG-CoA reductase. This interaction results in the ubiquitination of the enzyme. This modification and the presence of geranylgeraniol results in extraction of the enzyme from the membrane and degradation by the proteasome.

[Information from R. A. DeBose-Boyd. Feedback regulation of cholesterol synthesis: Sterol-accelerated ubiquitination and degradation of HMG CoA reductase, Cell Res. 18:609–621, 2008.]