Pharmacologically diverse HDAC inhibitors exist.7,8 Valproic acid [VPA] targets Class I [HDAC1–3 and 8] and Class IIa [HDAC4–5, 7 and 9] HDACs,9 and can restore pathologically low levels of histone-3 acetylation at lysine 27 [H3K27ac], a recognized surrogate marker of HDAC activity.10–12 Recently, we validated these observations in inflammatory bowel disease [IBD] patients, where active inflammation was associated with reduced H3K27ac.13 VPA inhibits fibrosis in numerous disease models,14–16 but its mechanism of action is unclear. The gene discussed is HDAC4; the disease is inflammatory bowel disease.