CIC (capicua transcriptional repressor) is a highly conserved transcriptional repressor that plays critical roles in neurodevelopment and disease. As a transcriptional repressor, CIC directly controls target genes involved in brain development, with pathogenic variants causing a spectrum of neurodevelopmental disorders including epilepsy, intellectual disability, autism spectrum disorder, and developmental delays 1. CIC functions as a negative regulator of cell-intrinsic immunity, with loss of CIC resulting in heightened antiviral responses 2. The protein is regulated through mitogen-activated protein kinase (MAPK) signaling and contributes to tumor progression through direct transcriptional control of effector target genes 3. CIC knockout leads to dysregulation of neurodevelopmental genes, including direct targets EPHA2 and ID1, which are linked to neurodevelopment and glioma tumorigenesis 4. In cancer, CIC alterations are particularly significant in rare sarcomas, where CIC-DUX4 fusions create aggressive undifferentiated round cell sarcomas with poor prognosis 5. Pediatric patients with CIC-fused sarcomas often present with large tumors and metastatic disease, showing dismal outcomes despite multimodal therapy 6. The protein's dual roles in neurodevelopment and oncogenesis highlight its importance as both a developmental regulator and tumor suppressor.