BCL9 (BCL9 transcription coactivator) functions as a critical component of the canonical Wnt/β-catenin signaling pathway, serving as a transcriptional coactivator that enhances β-catenin's transcriptional activity 1. The protein forms part of the β-catenin-TCF complex in the nucleoplasm, where it interacts with various signaling regulators and transcriptional machinery to regulate gene expression 1. BCL9 is frequently involved in oncogenic processes through chr1 rearrangements and copy number alterations. In acute lymphoblastic leukemia, MEF2D-BCL9 fusions represent the most common rearrangement among MEF2D-rearranged cases, resulting in enhanced transcriptional activity and poor clinical outcomes 2. Additionally, BCL9 copy number gains occur recurrently across multiple tumor types and are associated with HCC recurrence, leading to Wnt/β-catenin pathway activation and immune-excluded tumor microenvironments 34. The BCL9/β-catenin protein-protein interaction has emerged as a therapeutic target, with inhibitors showing promise in reversing immunotherapy resistance by modulating macrophage-mediated immune responses 56. These findings establish BCL9 as both a key mediator of Wnt signaling and a potential therapeutic target in cancer treatment.