LEO1 is a conserved component of the PAF1 complex (PAF1C) that associates with RNA polymerase II to regulate transcription elongation and RNA processing 1. LEO1 phosphorylation by CDK12 is essential for PAF1C association with elongating Pol II, and this phosphorylation is counterregulated by the Integrator-PP2A complex (INTAC) 1. The protein functions in multiple transcriptional processes including Hox and Wnt gene transcription, histone modifications, and mRNA 3' end formation 2. Additionally, LEO1 controls H3K9 methylation levels and is required for proper entry into cellular quiescence and regulation of gene expression in human fibroblasts 3. LEO1 partners with Cockayne syndrome protein B (CSB) in transcription-coupled DNA repair, being recruited to DNA damage sites and facilitating recovery of RNA synthesis following transcription-blocking lesions 4. Clinically, LEO1 is emerging as a neurodevelopmental disorder risk gene, with de novo variants identified in autism and intellectual disability cases 56. The gene has also been implicated in male infertility, with pathogenic variants identified in spermatogenic failure 2. LEO1 contributes to acute myelogenous leukemia progression through PRL-3-mediated upregulation, promoting oncogenic properties 7.