MBNL3 is an RNA-binding protein that functions as a splicing regulator with context-dependent activity 1. It promotes insulin receptor (IR) pre-mRNA exon 11 inclusion while repressing cardiac troponin T (cTNT) exon 5 inclusion in muscle 1. The functional domains mediating both splicing activation and repression are located within an 80-amino-acid regulatory region downstream of the N-terminal zinc-finger pair, distinct from the RNA-binding domains themselves 1. Among MBNL paralogs, MBNL3 exhibits the lowest splicing activity but is notably the most static and densely packed on pathogenic CUG expansion RNAs implicated in myotonic dystrophy 2. Beyond its classical role in muscle splicing, emerging evidence reveals MBNL3's involvement in cancer progression across multiple tumor types. In cholangiocarcinoma, high MBNL3 expression correlates with improved overall survival and modulates epithelial-mesenchymal transition (EMT), focal adhesion, and immune cell infiltration 3. Conversely, in gastric adenocarcinoma and pancreatic ductal adenocarcinoma, MBNL3 promotes cell proliferation, invasion, and angiogenesis through AKT/VEGFA pathway activation and metastatic potential 45. In leukemia, MBNL3 downregulation drives malignant reprogramming via reversion to embryonic splice isoforms, particularly CD44v3 overexpression 6. MBNL3 expression is also regulated by microRNAs (miR-302e, miR-302a) and transcription factors (TBP), modulating cancer-associated phenotypes 478.