ROR: Nuclear Receptor for Melatonin or Not?

Whether the retinoic acid-related orphan receptor (ROR) is a nuclear receptor of melatonin remains controversial. ROR is inextricably linked to melatonin in terms of its expression, function, and mechanism of action. Additionally, studies have illustrated that melatonin functions analogous to ROR ligands, thereby modulating the transcriptional activity of ROR. However, studies supporting these interactions have since been withdrawn. Furthermore, recent crystallographic evidence does not support the view that ROR is a nuclear receptor of melatonin. Some other studies have proposed that melatonin indirectly regulates ROR activity rather than directly binding to ROR. This review aims to delve into the complex relationship of the ROR receptor with melatonin in terms of its structure, expression, function, and mechanism. Thus, we provide the latest evidence and views on direct binding as well as indirect regulation of ROR by melatonin, dissecting both viewpoints in-depth to provide a more comprehensive perspective on this issue.

Automated summary

This review delves into the complex relationship between the ROR receptor and melatonin in terms of structure, expression, function, and mechanism. While studies initially suggested that melatonin functions analogous to ROR ligands, some studies have been withdrawn and recent crystallographic evidence does not support the view that ROR is a nuclear receptor of melatonin. Other studies propose that melatonin indirectly regulates ROR activity rather than directly binding to ROR.