ZBTB11 is a zinc finger and BTB domain-containing transcription factor that functions as a multifaceted regulator of cell fate, metabolism, and differentiation. In pluripotent cells, ZBTB11 maintains embryonic stem cell identity by repressing pro-differentiation genes through prevention of premature transcriptional elongation 1. The protein localizes to the nucleus and nucleolus, where it binds to gene promoters involved in ribosomal RNA synthesis and mitochondrial functions 2. ZBTB11 plays opposing roles in cancer contexts. In lung cancer, ZBTB11 promotes metastasis via SET-complex-mediated activation of matrix metalloproteinase-9 (MMP9) and transcriptional repression of PRRG2, driving YAP1-dependent invasion 3. Conversely, in pancreatic cancer, ZBTB11 upregulation drives KRAS inhibitor resistance through metabolic reprogramming toward oxidative phosphorylation; ZBTB11 degradation resensitizes resistant tumors 4. Biallelic ZBTB11 mutations cause autosomal recessive intellectual developmental disorder (MRT69), characterized by regional brain atrophy and mitochondrial dysfunction 5, consistent with ZBTB11's role in regulating mitochondrial gene expression 2. In cardiac pathology, ZBTB11 induction in cardiomyocytes triggers autophagy and apoptosis during arrhythmogenic cardiomyopathy 6. Additionally, ZBTB11-AS1 long noncoding RNA varies during HIV-1 infection stages in microglia 7.