It is currently unclear whether oxysterols are active players or bystanders in NASH pathogenesis, but some arguments for an active role have been put forward: In a murine model of NASH, the inhibition of 27-HC synthesis (due to knockdown of the enzyme CYP27A1) resulted in stronger NASH activity compared with wild-type and subcutaneous application of 27-HC, which substantially decreased liver inflammation (15). This evidence concerns the gene CYP27A1 and metabolic dysfunction-associated steatohepatitis.