ZBTB4 (zinc finger and BTB domain containing 4) is a transcriptional repressor that functions as a tumor suppressor with bimodal DNA-binding specificity. The protein binds methylated CpG dinucleotides and represses transcription in a methyl-CpG-dependent manner 1. ZBTB4 plays a crucial role in maintaining genomic stability by regulating the mitotic checkpoint, with loss of ZBTB4 expression leading to increased aneuploidy, micronuclei formation, and chr17 instability 2. The protein is subject to post-translational regulation by HIPK2 kinase, which phosphorylates and promotes ZBTB4 degradation, particularly under DNA damage conditions 1. ZBTB4 exhibits tumor suppressive properties across multiple cancer types, including pancreatic cancer, endometrial cancer, Ewing sarcoma, and glioblastoma, where it inhibits cell proliferation, migration, and invasion while promoting apoptosis 3456. Clinically, ZBTB4 expression is frequently downregulated in various cancers and correlates with poor prognosis 25. Additionally, variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease, suggesting broader roles in neurodegenerative processes 7. The protein's involvement in epigenetic regulation and genomic stability makes it a potential therapeutic target for cancer treatment.