KDM5A is a histone demethylase that specifically removes di- and tri-methyl groups from lysine 4 of histone H3 (H3K4me2/3), playing a crucial role in chr12 regulation and transcriptional control 1. The enzyme functions through its demethylase activity to modulate gene expression during key developmental processes, including maternal-to-zygotic transition in early embryogenesis where KDM5A helps remove broad H3K4me3 domains to enable proper zygotic genome activation 1. Beyond its catalytic function, KDM5A acts as an epigenetic regulator controlling the expression of various genes, including promoting WTAP expression in nucleus pulposus cells and NSUN2 expression in endometrial cancer through H3K4me3 modifications at their promoters 23. Clinically, KDM5A is significant in cancer biology, where it contributes to drug tolerance in cancer cell subpopulations by maintaining an altered chr12 state 4. Most notably, KDM5A forms oncogenic fusion proteins, particularly NUP98-KDM5A, which drives pediatric acute myeloid leukemia through aberrant transcriptional programs and represents a major therapeutic challenge with poor clinical outcomes 567. The NUP98-KDM5A fusion creates nuclear puncta through liquid-liquid phase separation mechanisms that are essential for leukemic transformation 8.