HDAC11 (histone deacetylase 11) is the sole class IV member of the histone deacetylase family that catalyzes deacetylation of lysine residues on core histones (H2A, H2B, H3, H4), functioning as an epigenetic repressor of gene expression 1. Beyond canonical histone deacetylation, HDAC11 regulates diverse cellular processes through non-histone substrates, including ERG acetylation 2 and AKAP12 myristoylation 3. In cancer biology, HDAC11 is significantly overexpressed in hepatocellular carcinoma, breast cancer, and renal urothelial carcinoma, where it promotes cancer stemness by suppressing LKB1 transcription and activating glycolytic metabolism through reduced AMPK signaling 4. HDAC11 inhibition enhances sorafenib sensitivity in kinase-resistant HCC, positioning it as a therapeutic target 4. In metabolic disease, HDAC11 overexpression contributes to hepatic lipid accumulation in MASLD, while selective HDAC11 inhibitors promote fatty acid oxidation via AMPK phosphorylation 5. HDAC11 suppresses thermogenesis in adipocytes by demyristoylating gravin-α; its inhibition independently drives UCP1 expression even under catecholamine resistance 3. In cardiovascular pathology, HDAC11 promotes endothelial pyroptosis through NLRP3/caspase-1 and caspase-3 pathways, implicating it in atherosclerosis progression 2. HDAC11 expression is also aberrantly methylated in Balkan endemic nephropathy, suggesting roles in genetic disease susceptibility 6.