Histone deacetylases: Emerging targets in dermatology

Abstract Posttranslational modifications, particularly histone acetylation and deacetylation, regulated by histone acetyltransferases and histone deacetylases (HDACs), play a fundamental role in the epigenetic regulation of gene expression by modulating chromatin structure and accessibility. HDACs are involved in diverse cellular processes, including cell cycle regulation, differentiation, apoptosis, immune responses, and metabolism. Dysregulation of HDAC activity has been implicated in the pathogenesis of various diseases, notably several dermatological conditions. Emerging evidence from preclinical and clinical studies highlights the role of HDACs in diseases such as psoriasis, scleroderma, atopic dermatitis, vitiligo, and cutaneous malignancies. In these disorders, HDACs influence critical pathological mechanisms, including keratinocyte proliferation, fibroblast activation, inflammatory signaling, autoimmune responses, and apoptosis of malignant cells. HDAC inhibitors (HDACis) represent a novel class of epigenetic therapeutics that have demonstrated potential in modulating these disease processes. This review aims to comprehensively assess the biological functions of HDACs in dermatological diseases and evaluate the therapeutic prospects of HDACis. Understanding the epigenetic mechanisms mediated by HDACs could pave the way for innovative treatment strategies in dermatology.