Histone deacetylase 11 (HDAC11) (HDAC11)

Histone deacetylase 11 (HDAC11) is the sole member of the Class IV histone deacetylase family and is the most recently identified HDAC isoform [1, 2]. Unlike other HDACs, HDAC11 possesses exceptionally high fatty acid deacylase activity, being over 10,000 times more efficient at removing long-chain acyl groups than acetyl groups from lysine residues [3, 8, 21]. It is primarily localized in the nucleus and cytoplasm of various tissues, including the brain, heart, kidney, and skeletal muscle [1, 3]. HDAC11 plays a critical role in regulating immune responses by acting as a negative regulator of interleukin-10 (IL-10) production and is also a key modulator of metabolic processes, including adipogenesis and thermogenesis [2, 5, 9, 11]. In disease contexts, HDAC11 is frequently overexpressed in various cancers, such as Hodgkin lymphoma and non-small cell lung cancer, where it contributes to tumor growth and immune evasion [1, 10, 12]. It is also implicated in metabolic disorders like obesity and type 2 diabetes, where its inhibition has been shown to increase energy expenditure and improve insulin sensitivity [2, 4, 9]. Therapeutic targeting of HDAC11 is an active area of research, with selective inhibitors like Elevenostat and FT895 being developed to minimize the systemic toxicities—such as hematological and cardiac issues—associated with pan-HDAC inhibitors [2, 16, 17]. As a biomarker, HDAC11 expression levels are used to predict prognosis and immune infiltration in several cancer types [10, 12, 15].

Other names

Class IV HDAC [1, 2, 3]HD11 [14]Histone deacetylase 11 [1, 14]

Histone deacetylase inhibition, fatty acid deacylase inhibition, and epigenetic regulation of gene expression [13, 14, 21].