According to rodent models, TLX is required to maintain NSCs in an undifferentiated proliferating state and its mutations cause disruption of neurogenesis in NSCs . In mice and drosophila, TLX knockout results in severe aggressiveness, abnormal brain development and retinal dystrophies . Moreover, TLX appears to play a crucial role in spatial learning and cognitive functions during adolescence and adulthood . Therefore, dysregulation of TLX has been associated with mental illness including bipolar disorders and schizophrenia . Beyond these roles in neurological homeostasis and brain function, recent reports have suggested a potential tumorigenic activity of the orphan NR due to marked overexpression in glioblastoma and neuroblastoma cell lines . These lines of evidence suggest TLX as an attractive target for neurodegenerative diseases and malignant brain tumors. Endogenous TLX ligands, forming an essential part of the NR function, remain elusive and only few synthetic TLX modulators with limited potency have been described to date . In light of its obvious therapeutic potential, further evaluation of the receptor's function and the discovery of potent TLX ligands are imperative.