Cholesterol and the development of clear-cell renal carcinoma

► The RCC clear cell phenotype represents deregulated lipid and cholesterol synthesis. ► Obesity and mevalonate pathway activation play a role in RCC development. ► TRC8 degrades preSREBP1/2 and HMGCR to inhibit the mevalonate pathway. ► Two hereditary RCC genes, TRC8 and FLCN, inhibit cholesterol/lipid biosynthesis.