Oxysterols: Old Tale, New Twists

Oxysterols have long been known for their important role in cholesterol homeostasis, where they are involved in both transcriptional and posttran-scriptional mechanisms for controlling cholesterol levels. However, they are increasingly associated with a wide variety of other, sometimes surprising cell functions. They are activators of the Hedgehog pathway (important in embryogenesis), and they act as ligands for a growing list of receptors, including some that are of importance to the immune system. Oxysterols have also been implicated in several diseases such as neurodegenerative diseases and atherosclerosis. Here, we explore the latest research into the roles oxysterols play in different areas, and we evaluate the current evidence for these roles. In addition, we outline critical concepts to consider when investigating the roles of oxysterols in various situations, which includes ensuring that the concentration and form of the oxysterol are relevant in that context-a caveat with which many studies have struggled.