Nr6a1, also known as Nuclear Receptor subfamily 6 group A member 1, is an orphan nuclear receptor with no close evolutionary homologs. It has emerged as a key regulator in various biological processes. Nr6a1 is involved in controlling the expression of key pluripotency and developmental genes. It is also associated with pathways like WNT, MTOR, MAPK and NOTCH, which play crucial roles in histone lysine lactylation (Kla) process in hepatocellular carcinoma (HCC) [1,2].

In mouse models, Nr6a1 was found to be a master regulator of trunk development, controlling vertebral number and segmentation of the trunk region, and was essential for the timely progression of Hox signatures, as well as neural versus mesodermal cell fate choice within axial progenitors [3]. In HepG2 cells, knockdown of Nr6a1 led to increased lipid accumulation, insulin-induced proliferation and migration, indicating its role in lipid metabolism regulation [5]. In mice, increased hippocampal Nr6A1 impaired CREB-BDNF signaling and led to depression-like behaviors [4]. Also, in zebrafish, knockdown of Nr6A1 paralogs resulted in abnormal eye and somite development [6,7].

In summary, Nr6a1 is vital for multiple biological functions including development, metabolism, and behavior-related processes. Model-based research, especially with mouse and zebrafish models, has revealed its significant roles in various disease-related areas such as HCC, depression, and a novel oculo-vertebral-renal (OVR) syndrome. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.