BRAT1 is a multifunctional protein with critical roles in RNA processing and DNA damage response. As a component of the Integrator complex, BRAT1 associates with INTS9 and INTS11 to regulate assembly of the RNA endonuclease module, blocking INTS11 active site activity until nuclear import and complex maturation occur 1. BRAT1 facilitates nuclear translocation of the INTS9-INTS11 heterodimer, with final release triggered by inositol hexakisphosphate binding 1. This Integrator function is essential for transcriptional regulation of neurodevelopmental genes, particularly those controlling neural differentiation 2. Beyond RNA processing, BRAT1 activates DNA damage response kinases (ATM, SMC1A, PRKDC) following ionizing radiation stress and regulates mitochondrial homeostasis and cell proliferation 3. Loss of BRAT1 increases glucose metabolism and mitochondrial reactive oxygen species production while suppressing Akt/Erk signaling 3. Pathogenic BRAT1 mutations cause neurodevelopmental disorders with variable severity, ranging from mild cerebellar atrophy and intellectual disability to lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) 4. Homozygous mutations typically present more severe phenotypes than compound heterozygotes 5. These findings establish BRAT1 as a critical integrator of transcriptional regulation and cellular stress responses essential for neurological development.