HDAC11

HDAC11 is the sole member of class IV histone deacetylases and represents the smallest zinc-dependent HDAC isoform, with distinctive catalytic properties that differentiate it from other HDAC family members^[1][2]. Mechanistically, HDAC11 functions as an epigenetic regulator that controls gene expression through deacylation and deacetylation reactions, and accumulating evidence indicates that its long-chain fatty acid defatty-acylase activity is substantially more efficient than its intrinsic deacetylase activity^[3][1]. Therefore, HDAC11 influences multiple biological pathways involved in immune regulation, metabolism, and cellular homeostasis^[1][4]. In immune signaling, HDAC11 regulates interleukin-10 expression, immune tolerance, and type I interferon signaling, highlighting its role as a key modulator of inflammatory responses^[5][6][7]. In metabolic systems, HDAC11 participates in adipogenesis, lipid metabolism, energy expenditure, and insulin-related processes, linking the enzyme to obesity and metabolic syndrome models^[4][8]. Disease-associated studies further demonstrate involvement of HDAC11 in cancer, neuroinflammation, and immune-mediated disorders, supporting its relevance as a therapeutic target across diverse experimental settings^[1][9]. Compared with related HDAC isoforms, HDAC11 exhibits unique substrate specificity and prominent defatty-acylase activity, providing a functional distinction that has stimulated intensive drug-discovery efforts^[1][3]. For experimental applications, several selective HDAC11 inhibitors have been developed and are widely used as chemical probes to investigate HDAC11-dependent pathways and evaluate therapeutic potential in disease models^[1][10].