ZBTB38 is a transcriptional regulator with dual DNA-binding specificity that functions as both a tumor suppressor and methylation-dependent transcription factor. The protein binds preferentially to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' but can also recognize E-box elements, repressing transcription in a methyl-CpG-dependent manner 1. ZBTB38 plays a critical role in DNA replication regulation by repressing MCM10 expression, which is essential for maintaining common fragile site stability 2. In cancer contexts, ZBTB38 functions as a tumor suppressor, with lower expression observed in prostate cancer tissues correlating with poorer prognosis 3. The protein suppresses cancer cell proliferation and migration by directly promoting DKK1 expression, inhibiting the WNT signaling pathway 3. Beyond cancer, ZBTB38 demonstrates tissue-specific functions, including regulation of anti-inflammatory responses through IL1r2 repression in rheumatoid arthritis 4 and influence on growth parameters, with genetic variants associated with idiopathic short stature and treatment response 2. The protein's unique genomic distribution includes binding sites in closed chr3 regions not occupied by other transcription factors, highlighting its specialized role in methylation-dependent gene regulation 1.