Hydroxymethylglutaryl‐coenzyme A reductase degradation occurs in the endoplasmic reticulum, and is regulated by the mevalonate pathway. In order to discover the molecules that mediate the degradation process and its control, we conducted a genetic analysis of the degradation of the yeast Hmg2p isozyme of hydroxymethylglutaryl‐coenzyme A reductase. Hmg2p degradation occurs by the action ofHRDgenes that direct Hmg2p to the ubiquitin‐proteasome pathway. Regulation ofHRD‐dependent Hmg2p degradation appears to occur by the action of a separate set of CRD genes. Curr Opin Lipidol 9:93–97. © 1998 Rapid Science Ltd