Testicular nuclear receptor 4 (TR4), also known as NR2C2 (nuclear receptor subfamily 2, group C, member 2), is a transcriptional factor and a member of the nuclear receptor family and shares high homology with the testicular nuclear receptor 2. TR4 was initially cloned from human and rat hypothalamus, prostate, and testes libraries. TR4 binds to a direct repeat regulatory element in the promoter of a variety of target genes and plays a key role in tumorigenesis, lipoprotein regulation, and central nervous system development. Testicular nuclear receptor 4 (TR4) could function as a suppressor in the transcriptional regulation of the HBV core gene expression, which might then influence the development of hepatocellular carcinoma (HCC). The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important in the control of energy homeostasis.