KDM4D is a histone demethylase that specifically removes methyl groups from lysine-9 of histone H3 (H3K9), generating formaldehyde and succinate as byproducts 1. It demethylates both di- and trimethylated H3K9 residues but lacks activity on monomethylated forms, playing a central role in histone code regulation [UniProt]. KDM4D functions in multiple cellular contexts: it enhances osteo/dentinogenic differentiation and migration of stem cells from the apical papilla through interaction with ribosomal protein RPS5 2, and regulates H3K9me3 distribution in developing sperm, where its absence causes subfertility due to impaired sperm motility 3. In hepatocellular carcinoma, KDM4D forms a complex with β-catenin to activate MMP9 transcription, promoting immune escape and anti-PD-1 resistance 4. KDM4D is also implicated in disease pathogenesis: elevated expression correlates with pterygium development by promoting fibroblast proliferation and migration while inhibiting apoptosis 5, and strong KDM4D expression associates with radioresistance and aggressive phenotype in classical Hodgkin lymphoma 6. These findings establish KDM4D as a therapeutic target, with selective inhibitors and PROTAC degraders showing promise in preclinical cancer models 78.