KDM4E is a histone demethylase belonging to the Fe(II)/2-oxoglutarate-dependent family that catalyzes removal of methyl groups from histone lysine residues, thereby regulating epigenetic states and gene expression 1. Its primary function involves demethylating trimethylated histone H3 lysine 9 (H3K9me3) to monomethylated forms and demethylating H3K56me3, playing a central role in histone code regulation 23. KDM4E also demonstrates activity on linker histone H1 methylated residues, with particularly high efficiency 4. The enzyme exhibits oxygen-dependent activity across physiologically relevant concentrations, suggesting potential regulation by cellular oxygen availability 1. KDM4E is transcriptionally activated by the DUX4 transcription factor during cleavage-stage development and in FSHD-associated myocytes, representing a key target gene in developmental and pathological contexts 56. Clinically, KDM4E has emerged as therapeutically relevant in cancer and cardiac pathology; baicalein enhances KDM4E expression to suppress triple-negative breast cancer progression through BICD1-mediated PAR1 signaling inhibition 7, while dysregulation occurs in post-ischemic hearts where excessive branched-chain amino acids trigger KDM4E-dependent H3K9me3 loss, impairing mesenchymal stem cell survival 8. Selective KDM4E inhibitors represent promising anti-cancer agents under development 910.