INTS1 encodes the largest subunit of the Integrator complex, a multi-protein assembly that regulates RNA polymerase II (RNAPII) transcription termination and maintains transcriptional integrity 1. The protein functions as a quality checkpoint during transcription elongation by facilitating premature termination of unfavorably configured transcripts through dephosphorylation of RNAPII subunits and promoting nascent RNA degradation 1. INTS1 specifically participates in the post-termination step, displacing other complex components to reset the integrator for subsequent termination cycles. Biallelic variants in INTS1 cause a rare autosomal recessive neurodevelopmental disorder characterized by intellectual disability, congenital cataracts, growth retardation, and craniofacial dysmorphism 2 3. Recent studies have expanded the phenotypic spectrum to include severe sleep-wake cycle disruptions and circadian rhythm abnormalities 4. Zebrafish models demonstrate that INTS1 deficiency leads to abnormal lens development, disrupted circadian locomotor activity, and elevated dopamine β-hydroxylase expression in brainstem centers 2 4 1. The gene's role in transcriptional regulation makes it clinically significant for understanding neurodevelopmental pathways, and it has emerged as a potential biomarker in cancer detection assays 5.