KDM4C (lysine demethylase 4C) is a histone demethylase that specifically removes trimethyl marks from histone H3 lysine 9 (H3K9me3) and lysine 36 (H3K36me3), thereby regulating chr9 architecture and gene expression 1. The enzyme catalyzes demethylation through an α-ketoglutarate-dependent mechanism, generating formaldehyde and succinate as byproducts. KDM4C plays critical roles in multiple pathological contexts. In lung cancer, KDM4C overexpression promotes radioresistance by reducing H3K9me3 at the TGF-β2 promoter to activate pro-survival signaling 2. Mechanistically, the deubiquitinase USP9X stabilizes KDM4C protein levels 2. KDM4C also suppresses anti-tumor immunity by maintaining H3K36me3 at the CXCL10 locus, limiting CD8+ T cell infiltration; KDM4C inhibition enhances immunotherapy response 3. In acute myeloid leukemia, KDM4C regulates leukemia stem cell function by reducing H3K9me3 at the ALKBH5 locus to maintain m6A demethylase expression 4. In glioblastoma, Wnt signaling stabilizes KDM4C to activate target gene transcription 5, and KDM4C overexpression decreases radiosensitivity 6. Notably, in basal breast cancer, KDM4C inhibition triggers cathepsin L-mediated histone H3 proteolysis independent of canonical demethylase activity 7. Genome-wide association studies identify KDM4C variants associated with pubertal timing and age-related disease risk 8, suggesting broader developmental and metabolic roles.