Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications.

HDAC6 is integral to the regulation of primary cilia, which are specialized structures that serve as crucial signaling hubs for cellular communication and environmental response. These ciliary functions are essential for maintaining cellular homeostasis and orchestrating developmental processes. Dysregulation of HDAC6 activity is implicated in ciliopathies, a group of disorders characterized by defective ciliary structure or function, resulting in widespread organ involvement and significant morbidity. This review provides a comprehensive examination of the molecular dynamics of HDAC6 in the context of ciliogenesis and ciliopathies, emphasizing its dual role in the deacetylation of microtubules and regulation of the ciliary axoneme. Furthermore, HDAC6 interacts with key signaling molecules, modulating processes ranging from cell cycle regulation to inflammatory responses, which highlights its central role in cellular physiology and pathology. The therapeutic potential of HDAC6 inhibitors has been explored, with promising results in various disease models, including retinal and renal ciliopathies, highlighting their ability to restore normal ciliary function. This analysis not only underscores the critical importance of HDAC6 in maintaining ciliary integrity but also illustrates how targeting the HDAC6-cilia axis could provide a groundbreaking approach to treating these complex disorders. In doing so, this review sets the stage for future investigations into HDAC6-targeted therapies, potentially transforming the clinical management of ciliopathies and significantly improving patient outcomes.