INSIG2 and central nervous system cancer: Kucharzewska et al. also reported decreased cholesterol synthesis in hypoxic U87 glioma cells exposed to elevated levels of squalene, lathosterol, and lanosterol, as well as increased rates of degradation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the enzyme that catalyzes the rate-limiting step in the cholesterol synthesis pathway, via the ubiquitinase insulin-induced gene 2 (Insig2) [231] (Figure 4).