TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease

TLX (NR2E1), an orphan member of the nuclear receptor superfamily, is a transcription factor that has been described to be generally repressive in nature. It has been implicated in several aspects of physiology and disease. TLX is best known for its ability to regulate the proliferation of neural stem cells and retinal progenitor cells. Dysregulation, overexpression, or loss of TLX expression has been characterized in numerous studies focused on a diverse range of pathological conditions, including abnormal brain development, psychiatric disorders, retinopathies, metabolic disease, and malignant neoplasm. Despite the lack of an identified endogenous ligand, several studies have described putative synthetic and natural TLX ligands, suggesting that this receptor may serve as a therapeutic target. Therefore, this article aims to briefly review what is known about TLX structure and function in normal physiology, and provide an overview of TLX in regard to pathological conditions. Particular emphasis is placed on TLX and cancer, and the potential utility of this receptor as a therapeutic target.