Abstract: The sterol regulatory element-binding protein (SREBP) pathway controls cellular homeostasis of sterols through a negative feedback mechanism. SREBP-cleavage activating protein (SCAP), and insulin-induced gene-2 (INSIG-2), 25-hydroxycholesterol (25HC) play an important role in regulating the activation, maturation, and nuclear translocation of SREBP. Recent studies have shown the structure of the SCAP-INSIG-2-25HC complex, which is important to the study of intracellular cholesterol metabolism.