BCL6B is a sequence-specific transcriptional repressor belonging to the ZBTB (zinc finger and BTB domain-containing) protein family 1, located on chromosome 17.1 2. It functions as a transcriptional repressor involved in gene regulation and cellular proliferation, with ubiquitous tissue expression but abundant expression in heart and placenta 2. Mechanistically, BCL6B acts by binding to promoter regions of target genes, including ETV2 and Notch signaling components, to suppress their transcriptional activity 34. BCL6B expression is frequently regulated by epigenetic modifications, particularly promoter hypermethylation 56. BCL6B demonstrates critical roles in disease prevention and progression. In hepatocellular carcinoma, BCL6B functions as a tumor suppressor—its epigenetic silencing inactivates p53 signaling and promotes chemoresistance, while restoration activates p53 and sensitizes cells to 5-fluorouracil 5. Low BCL6B expression correlates with shorter overall survival and serves as an independent prognostic factor 7. In gastric cancer, BCL6B epigenetic inactivation amplifies inflammatory response, promoting carcinogenesis 6. BCL6B also suppresses endothelial differentiation by repressing ETV2 3 and inhibits ocular neovascularization through Notch signal silencing 48, making it a potential therapeutic target for ocular vascular diseases and hepatocellular carcinoma.