KANSL1 (KAT8 regulatory NSL complex subunit 1) is a non-catalytic component of the NSL histone acetyltransferase complex that mediates histone H4 acetylation at lysine-5 and lysine-8 (H4K5ac and H4K8ac) at transcription start sites, promoting transcription initiation 123. Beyond transcriptional regulation, KANSL1 regulates mitochondrial gene expression 4 and plays essential roles in spindle assembly and microtubule stability during mitosis 5. KANSL1 is critical for autophagy regulation, specifically modulating autophagosome-lysosome fusion through transcriptional control of STX17 6. KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), a rare neurodevelopmental disorder characterized by intellectual disability, cardiac dysfunction, hypotonia, and congenital malformations 67. A 17q21.31 duplication involving KANSL1 is associated with neurodevelopmental pathology 8, and functional regulatory variants in KANSL1 confer risk for progressive supranuclear palsy 9. Additionally, KAT6B/A::KANSL1 fusions drive a distinct uterine sarcoma entity with aggressive clinical potential 1011.