Cux2, also known as Cut-like homeobox 2, is a transcription factor that plays diverse roles in various biological processes. It controls neuronal proliferation, dendrite branching, and synapse formation, and is involved in limb positioning during development. It also has implications in several signaling pathways, such as those related to tumorigenesis and neurogenesis [4,5,6]. Genetic models, including KO mouse models, are valuable for studying its functions.

In cancer research, loss-of-function experiments show that CUX2 silencing significantly inhibits the proliferation, colony formation, migration, invasion, and promotes apoptosis in papillary thyroid cancer cells. CUX2 may act as an oncogene by inducing epithelial-mesenchymal transition and influencing the phosphorylation of AKT and mTOR in the PI3K-AKT-mTOR pathways [3]. In breast cancer, inhibition of CUX2 suppresses cell malignant phenotypes through the KDM5B/SOX17 axis. CUX2 promotes KDM5B expression, which in turn inhibits SOX17 expression [1]. In gliomas, overexpression of CUX2 represses the proliferative, migrating, and invasive abilities of glioma cells by enhancing ADCY1 transcription [2]. In epilepsy research, Cux2-specific knockout mice show high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and enhanced glutamatergic synaptic transmission to the hippocampus, suggesting that CUX2 variants may contribute to temporal lobe epilepsy pathology [4].

In conclusion, Cux2 is crucial for normal development and physiological function. Model-based research, especially KO mouse models, has revealed its significance in cancer and epilepsy. Understanding Cux2's functions can provide insights into the mechanisms of these diseases, potentially leading to new therapeutic strategies.