HDAC10 is a class IIb histone deacetylase with dual enzymatic functions, though its primary physiological role remains incompletely characterized. Unlike most HDACs, HDAC10 functions predominantly as a polyamine deacetylase, exhibiting high specificity for N8-acetylspermidine deacetylation while showing attenuated activity toward other acetylated polyamines 1. Although histone deacetylase activity has been demonstrated in vitro, the physiological relevance of this protein-deacetylating function remains unclear 1. Mechanistically, HDAC10 employs a zinc-activated water molecule for catalysis within a sterically constrained active site that enforces substrate specificity 1. Recent studies reveal HDAC10 directly deacetylates NLRP3 at the K496 residue, switching it from acetylation to ubiquitination-mediated proteasomal degradation, thereby inhibiting NLRP3 inflammasome activation 2. Additionally, HDAC10 controls MYC-dependent transcriptional induction of the DNA polymerase POLD1, maintaining DNA replication processivity and genome integrity in lymphoid cells 3. Clinically, HDAC10 inhibition shows therapeutic potential in cancer treatment. Tucidinostat, a selective HDAC10 inhibitor, has been approved in Asia for multiple carcinomas including cervical cancer, T-cell lymphoma, and breast cancer 4. HDAC10 also plays roles in autophagy promotion and mismatch repair, with emerging recognition as a biomarker for cancer therapeutics 1.