Processes that regulate energy expenditure have been the subject of intense study in recent years, both for their physiological importance and for their potential to be targeted for the treatment of metabolic diseases.De novo cholesterol synthesis from acetyl-CoA involves many steps and is an energetically costly pathway.Previous studies have shown that inhibition of cholesterol synthesis improves metabolic diseases (Tang et al., 2011;Liu et al., 2012;Zhang et al.,2017).But how the cholesterol synthesis pathway is linked to energy expenditure remains poorly understood.In a recent study published in Nature, Lu et al.identified ubiquitinspecific peptidase 20 (USP20) as a deubiquitylase that stabilizes HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis.Inhibition of USP20 was shown not only to reduce cholesterol synthesis through HMCGR degradation, but also to increase energy expenditure through succinate production (Lu et al., 2020).