HDAC10

HDAC10 (histone deacetylase 10) is a zinc-dependent class IIb histone deacetylase that functions primarily as a polyamine deacetylase, representing a distinct enzymatic activity within the HDAC family^[1]. Mechanistically, HDAC10 regulates polyamine metabolism and contributes to cellular homeostasis through pathways linked to autophagy and lysosomal function, making it an important epigenetic regulator beyond canonical histone deacetylation^[1][2]. In disease-related studies, HDAC10 has attracted considerable interest in cancer biology, where altered HDAC10 activity has been associated with tumor-relevant cellular processes and therapeutic response mechanisms^[2][3]. Experimental evidence further indicates that pharmacological or genetic inhibition of HDAC10 can promote autolysosome accumulation in neuroblastoma models, supporting a functional connection between HDAC10 and autophagy regulation^[3][4]. Compared with its closest class IIb homolog HDAC6, HDAC10 exhibits unique substrate selectivity and is currently recognized as the only identified HDAC family member with established polyamine deacetylase activity, highlighting a major functional distinction between these related isoforms^[1][2]. Structural studies have identified characteristic features, including the acidic gatekeeper residue Glu274, that contribute to substrate recognition and isoform selectivity^[4]. For experimental applications, the development of selective HDAC10 inhibitors has enabled more precise interrogation of HDAC10-dependent biology, and recent compounds have demonstrated high selectivity over HDAC6 while serving as valuable chemical probes for investigating autophagy, cancer-associated pathways, and polyamine-dependent cellular processes^[1][4].