ASH2L (ASH2 like, histone lysine methyltransferase complex subunit) is a core component of SET1/MLL histone methyltransferase complexes that regulates transcription by catalyzing H3 lysine 4 methylation 1. As part of the MLL1/MLL complex, ASH2L mediates mono- and trimethylation at histone H3 lysine 4, specifically blocking methylation when the neighboring lysine 9 is already modified 2. ASH2L functions as a transcriptional regulator through recruitment of histone methyltransferase complexes to gene promoters 3. In association with RBBP5 and WDR5, it stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A, and SETD1B 4. ASH2L dysfunction is implicated in multiple disease contexts. ASH2L deficiency drives pulmonary vascular remodeling in pulmonary hypertension through non-canonical mechanisms involving KLF5-NOTCH3 signaling 5. ASH2L-K312 lactylation promotes hepatocellular carcinoma malignancy by enhancing VEGFA expression and angiogenesis 6. In glioblastoma, ASH2L depletion reduces cell viability through downregulation of cell cycle regulatory genes 7. Additionally, ASH2L aggravates diabetic nephropathy by promoting HIPK2 expression and subsequent fibrosis and inflammation 8. These findings suggest ASH2L as a potential therapeutic target across multiple disease types.