KDM7A is a Jumonji C domain-containing histone demethylase that catalyzes removal of mono- and di-methyl groups from multiple histone lysine residues 1. It specifically demethylates H3K9me2, H3K27me2, H3K36me2, and H4K20me1 23, with activity modulated by H3K4me3 binding, which suppresses H3K9me2 demethylation while enhancing H3K27me2 activity 2. KDM7A is essential for normal brain development and neuronal differentiation 1. Beyond developmental roles, KDM7A functions in disease-relevant processes. In breast cancer, KDM7A maintains cancer stem cell populations by upregulating stemness factors KLF4 and c-MYC while inhibiting apoptosis through BCL2 upregulation 4. In pancreatic cancer, G9a orchestrates KDM7A downregulation to promote H3K27 methylation and epithelial-mesenchymal transition 5. KDM7A also regulates cetuximab resistance in head and neck squamous cell carcinoma through nuclear miR-451a-mediated transcriptional activation 6. More broadly, KDM7A suppresses fibrotic macrophage polarization via H3K27me2-mediated repression of TLR8, with declining expression associated with age-related fibrosis susceptibility 7. Inhibition of KDM7A restores protective H3K79 methylation and prevents osteoarthritis progression 8. These findings establish KDM7A as a therapeutic target across multiple diseases.