Insig regulates SCAP–SREBP movement. In the presence of cholesterol, Insig interacts with SCAP–SREBP and prevents the activation of SREBP. Cholesterol binding to SCAP or 25-hydroxycholesterol binding to Insig facilitates the interaction of Insig and SCAP, retaining SCAP–SREBP in the endoplasmic reticulum.

[Information from M. S. Brown and J. L. Goldstein. Cholesterol feedback: From Schoenheimer’s bottle to Scap’s MELADL, J. Lipid Res. 50:S15–S27, 2009.]