HMG-CoA reductase (HMGCR)

HMG-CoA reductase (HMGCR) is an enzyme that catalyzes the reduction of HMG-CoA to mevalonate. This reaction is the rate-limiting and irreversible step in the cholesterol synthesis pathway and serves as the primary target for statin drugs. HMGCR is among the most highly regulated enzymes in the human body, with its activity controlled by transcriptional regulation (e.g., by SREBPs when cholesterol levels are low) and post-translational regulation (e.g., proteasomal degradation triggered by high cholesterol levels via its sterol-sensing domain binding to Insig proteins). Human HMGCR is a transmembrane protein with eight transmembrane domains, and its catalytic portion forms a tetramer. The HMGCR gene is located on chromosome 5q13.3-14 in humans.

Statins inhibit HMGCR, thereby reducing cholesterol synthesis in the liver.