HDAC1 is a histone deacetylase that catalyzes lysine deacetylation on core histones (H2A, H2B, H3, H4), establishing epigenetic repression marks critical for transcriptional regulation, cell cycle progression, and development 1. HDAC1 functions within multiprotein complexes, including the NuRD chr1 remodeling complex 2 and SIN3B complex, where it regulates histone acetylation at transcribed regions 3. Beyond histones, HDAC1 deacetylates non-histone proteins including RELA, SP1, SP3, and STAT3, modulating their transcriptional activities 4. HDAC1 also exhibits protein-lysine deacylase activity, performing decrotonylation and delactylation of histones 5. Clinically, HDAC1 dysfunction associates with multiple diseases. In colorectal cancer, HDAC1 lactylation regulates ferroptosis resistance through FSP1 mRNA degradation pathways 6. HDAC1 controls dendritic cell development and anti-tumor immunity by regulating transcription factors IRF4, IRF8, and SPIB; HDAC1 deletion enhances cDC2 maturation and CD8+ T cell-mediated immunity 7. In diabetic kidney disease, HDAC1 inhibition restores autophagy and alleviates endothelial-mesenchymal transition via PI3K/AKT/mTOR pathway suppression 8. HDAC1 also modulates drug resistance in lung adenocarcinoma and regulates host-pathogen interactions during Leishmania infection 910. Additionally, HDAC1 mediates anti-inflammatory responses to anesthetic isoflurane in monocytes through NF-κB regulation 11.