ZBTB2 (zinc finger and BTB domain containing 2) is a transcriptional regulator with dual functions depending on cellular context. The protein contains an N-terminal BTB/POZ domain that enables homodimerization and a C-terminal zinc finger region for DNA binding 1. ZBTB2 functions as a transcriptional repressor through recruitment of histone deacetylases (HDACs) to target promoters, including HIV-1 and RelA/p65, leading to chr6 modifications and gene silencing 23. The protein partners with the NuRD chr6 remodeling complex to mediate its repressive functions 4. However, ZBTB2 also acts as a transcriptional activator, particularly for HIF-1 target genes under hypoxic conditions, where homodimerization is required for full activation 15. Disease relevance includes roles in cancer progression, where ZBTB2 promotes malignant phenotypes in p53-deficient tumors by activating HIF-1 signaling 1, and in gastric cancer where it acts as an oncogene by repressing the ARF-HDM2-p53-p21 pathway 6. Clinically, ZBTB2 expression correlates with poor prognosis in lung cancer patients, and its regulation by the CUL3-ZBTB2 E3 ligase complex affects PARP inhibitor resistance in prostate cancer 17.