**8. Conclusion**

ERRs are a family of orphan NRs that do not have a known endogenous ligand. Of the three isoforms of ERRs (ERRα, ERRβ, and ERRγ), ERRα and ERRγ are involved in the transcriptional regulation of mitochondrial metabolism and integrity, OXPHOS, glucose and lipid metabolism metabolism, while ERRβ plays a role in embryonic development. The transcriptional activity of ERRs requires binding with coactivator PGC-1α. ERRs share overlapping functions with PGC-1α regulated transcriptional networks and are subjected to the factors that regulate PGC-1α. In addition, ERRs are regulated post-translationally by upstream signal that also include the insulin regulated PI3K/AKT signaling pathways. In recent years, a major development in the cellular functions regulated by ERRs is the discovery of lipogenesis and glycerolipid biosynthesis regulation by ERR. These functions of ERRs allow them to play major roles in NAFLD/NASH development. Pharmacologically, significant efforts have been put forth to identify ligands for ERRs and these studies identified several agonists and antagonists for ERRs that can be further developed for future therapeutical efforts. Notably, DBD antagonists are also being developed and shown strong promise at targeting NAFLD. This review provides a brief and comprehensive view for the transcriptional network regulated by ERRs and their functions in NAFLD and potential therapeutical developments targeted at ERRs.
