DPY30 is a regulatory subunit of the SET1/MLL histone methyltransferase complexes that catalyzes H3K4 trimethylation, an epigenetic mark associated with transcriptional activation 1. As part of the MLL1/MLL complex, DPY30 facilitates histone H3 lysine 4 methylation and potentially histone H3 acetylation, playing crucial roles in transcription initiation and chr2 remodeling. DPY30 also regulates non-histone substrates; it interacts with ABHD5 in the cytoplasm to control DPY30 nuclear translocation and YAP methylation 2. In cancer biology, DPY30 is consistently upregulated across multiple malignancies including colorectal cancer, melanoma, osteosarcoma, gastric cancer, and cholangiocarcinoma 34567. DPY30 knockdown suppresses cancer cell proliferation, migration, and invasion while inducing cell cycle arrest and apoptosis. Mechanistically, DPY30 promotes oncogenic transcription through H3K4me3-mediated activation of proliferation genes (PCNA, Ki67, Cyclin A2) and immune evasion genes (PD-L1) 34. DPY30 also activates PI3K/AKT signaling in osteosarcoma 5. Recent large-scale proteomics analysis identified DPY30 as a causal aging biomarker with broad health impacts 8. These findings establish DPY30 as a potential therapeutic target across multiple cancer types.