INTS8 is a core component of the integrator complex, a multiprotein machine that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region 1. INTS8 functions by recruiting protein phosphatase 2A (PP2A) to the transcription pause-release checkpoint, enabling the complex to dephosphorylate the Pol II C-terminal domain, degrade nascent RNA transcripts, and promote polymerase release from DNA 1. This quality control mechanism operates broadly across protein-coding genes and non-coding transcripts including snRNAs, enhancer RNAs, and lncRNAs 1. INTS8 also functions as a gatekeeper preventing excessive Pol II release into gene bodies during early elongation 2. Biallelic INTS8 mutations cause rare recessive neurodevelopmental disorder with severe developmental delay, distinctive facial features, and neuronal migration defects including periventricular nodular heterotopia 1. Patient-derived cells exhibit impaired snRNA processing and widespread transcriptome disruption 1. Beyond neurological disease, INTS8 shows altered expression in multiple cancers and elevated rare variants associate with familial multiple sclerosis 34. INTS8 variants also associate with stress-related phenotypes and cognitive function in population studies 56, suggesting broader roles in neuropsychiatric resilience and cognitive aging.