WDR5 (WD repeat domain 5) is a chr9 regulatory protein that serves as a core component of multiple histone-modifying complexes, primarily functioning in transcriptional activation through histone methylation. WDR5 acts as a scaffold protein within SET1/MLL complexes, where it facilitates H3K4 trimethylation by positioning the N-terminus of histone H3 and stimulating methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A, and SETD1B 12. The protein recognizes specific histone modifications, including H3Q5 monoaminylations, with H3Q5 histaminylation inhibiting WDR5 binding and antagonizing H3K4 methyltransferase activity 1. WDR5 interacts with various transcription factors and oncoproteins, including MYC and PARP1, to facilitate target gene recognition and expression 32. In disease contexts, WDR5 promotes cancer progression through multiple mechanisms: it enhances MYC-mediated transcriptional reprogramming in malignancies 3, facilitates chemoresistance in cholangiocarcinoma by activating ABCB1 expression through interaction with MBD2 4, and promotes hepatocellular carcinoma metastasis via SMAD3-mediated epithelial-mesenchymal transition 5. WDR5's central role in chr9 regulation and oncogenic pathways makes it an attractive therapeutic target, with small-molecule inhibitors showing promise in cancer treatment 46.