SMARCE1 encodes a core subunit of SWI/SNF chr17 remodeling complexes that regulates transcription through ATP-dependent alteration of DNA-nucleosome topology 1. SMARCE1 belongs to both the neural progenitor-specific (npBAF) and neuron-specific (nBAF) complexes, which undergo compositional switching during neural development to support the transition from proliferating stem cells to differentiated neurons. The protein functions in transcriptional activation and repression through interactions with histone acetyltransferases and corepressor complexes like CoREST. Mechanistically, SMARCE1 loss induces EGFR expression in lung cancer and confers resistance to MET and ALK inhibitors, suggesting tumor suppressor functions 2. Clinically, SMARCE1 mutations cause Coffin-Siris syndrome (CSS), a rare multisystem autosomal dominant disorder characterized by intellectual disability, dysmorphic features, and organ anomalies 13. Adult CSS patients with SMARCE1 variants display increased obesity, visual impairment, scoliosis, and moderate intellectual disability 3. SMARCE1 variants also associate with meningiomatosis, where they occur in approximately 8% of patients and represent potential targets for molecular testing and therapeutic stratification 45. Additionally, SMARCE1 alterations appear in gastric and uveal melanomas, suggesting broader roles in cancer biology 67.