KDM4B (lysine demethylase 4B) is a histone-modifying enzyme that specifically demethylates trimethylated and dimethylated lysine 9 on histone H3 (H3K9me3/2), playing crucial roles in gene expression regulation and chr19 remodeling 1. The enzyme functions by removing repressive H3K9me3 marks, thereby activating gene transcription and coordinating β-catenin/Smad1-mediated signaling pathways 2. KDM4B is essential for normal brain development, with high expression levels in the hippocampus during neurogenesis 1. Loss-of-function variants cause autosomal dominant intellectual developmental disorder 65, characterized by global developmental delay, language and motor impairments, seizures, and brain malformations including corpus callosum agenesis and hippocampal abnormalities 13. The protein also regulates mesenchymal stem cell fate decisions, promoting osteogenic differentiation while suppressing adipogenesis through DLX gene expression control 42. In cancer biology, KDM4B dysfunction contributes to DNA repair defects, as oncometabolites can inhibit KDM4B activity, leading to aberrant H3K9 hypermethylation at DNA break sites and impaired homologous recombination repair 5. These diverse functions make KDM4B a potential therapeutic target for both developmental disorders and cancer treatment 6.