<i>Sox10</i> induction partially rescued myelination deficits.<h4>Discussion</h4>These findings define a KDM6B→<i>SOX10</i> axis that promotes oligodendrocyte maturation and cortical myelination by restricting repressive H3K27me3, providing mechanistic insight into epigenetic control of myelination with relevance to KDM6B-associated neurodevelopmental disorders. The gene discussed is KDM6B; the disease is neurodevelopmental disorder.