CUX1 is a homeodomain transcription factor that plays multifaceted roles in development and disease. Functionally, CUX1 regulates cell cycle progression at the G1/S transition through proteolytic processing into a 110 kDa N-terminal truncated form (CDP/Cux p110) that stably binds DNA and activates genes like POLA1 1. CUX1 controls expression of genes involved in DNA replication, mitosis, and cell motility 1, while also regulating dendrite branching and synapse formation in cortical pyramidal neurons 1. Pathogenic heterozygous CUX1 variants cause neurodevelopmental disorder characterized by delayed speech and motor development, intellectual disability, seizures, and joint laxity 2. Mouse models demonstrate that haploinsufficiency reduces CUX1 protein expression and increases seizure susceptibility, though symptoms may ameliorate with age 2. CUX1 exhibits paradoxical roles in cancer: loss of heterozygosity or mutations function as tumor suppression, while genomic amplification and overexpression in advanced tumors correlate with poor prognosis 34. In myeloid malignancies, CUX1 loss on chromosome 7 cooperates with EZH2 inactivation to promote chemotherapy resistance through defective DNA damage response 56. Recent evidence reveals CUX1 exerts species-specific effects on adipogenesis, promoting human adipocyte differentiation while inhibiting mouse differentiation 7.