HDAC6, a class IIB HDAC isoenzyme, is unique in its structural and physiological functions. Unlike many other HDACs, it is primarily cytoplasmic. Besides histone modification, it targets several non-histone proteins such as Hsp90, α-tubulin, cortactin, HSF1, etc. HDAC6 is involved in different signaling pathways related to neurological disorders, cancers, rare diseases, immunological conditions, heart failure, and obesity [1].

In male HFpEF mouse models, inhibiting HDAC6 with TYA-018 reverses established heart failure and related symptoms. Male mice lacking the Hdac6 gene have delayed HFpEF progression and are resistant to TYA-018's effects [2]. In diet-induced obese mice, treatment with blood-brain barrier-permeable HDAC6 inhibitors reduces food intake and leads to weight loss, while genetic depletion of Hdac6 in AgRP-expressing neurons results in a lack of such anti-obesity effect [3]. In primordial follicle studies, overexpression of Hdac6 in a transgenic mouse model delays primordial follicle activation and prolongs the mouse reproductive lifespan [4].

In conclusion, HDAC6 plays crucial roles in multiple biological processes and disease conditions. The use of gene knockout or conditional knockout mouse models has revealed its significance in heart failure, obesity, and female fertility. Targeting HDAC6 shows potential as a therapeutic strategy for various diseases [2,3,4].