INTS11 is the catalytic RNA endonuclease subunit of the Integrator complex, a multiprotein assembly that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region 12. INTS11 executes a quality control checkpoint during transcription elongation by degrading nascent RNA transcripts through its metal-dependent endonucleolytic activity, while the Integrator complex simultaneously dephosphorylates Pol II and promotes its release from DNA 345. The complex regulates synthesis termination of both coding and non-coding transcripts, including enhancer RNAs, small nuclear RNAs, and long non-coding RNAs 16. INTS11 forms a functionally essential heterodimeric interaction with Integrator subunit 9 (INTS9) through conserved C-terminal domains, which is critical for snRNA 3'-end processing 26. Additionally, INTS11 requires cytoplasmic stabilization by binding partner BRAT1 for proper nuclear function 7. Bi-allelic INTS11 variants cause severe neurodevelopmental disorder characterized by global developmental and language delays, intellectual disability, motor impairment, and progressive brain atrophy 89. Loss-of-function INTS11 mutations impair catalytic activity, causing G2/M cell cycle arrest and dysregulation of neurogenesis-related genes including CDKL5, with reduced neural progenitor cell generation and increased apoptosis 10. Drosophila studies confirm INTS11 integrity is critical for brain development 8. At the molecular level, INTS11 and CDK9 have opposing functions in maintaining promoter directionality, with INTS11 terminating antisense transcription while CDK9 protects sense transcription 11.