KAT5, also known as TIP60, is a lysine acetyltransferase that plays a crucial role in various biological processes. It is involved in pathways such as autophagy, glycolysis, innate immune response, and DNA damage repair. KAT5 mediates acetylation and lactylation of key proteins, regulating their functions and participating in important cellular programs [1,3,4].

In myocardial ischemia-reperfusion injury (MIRI) models, KAT5 was downregulated, and its overexpression inhibited NLRP3-mediated cardiomyocyte pyroptosis to relieve MIRI through modulation of the STUB1/LATS2/YAP/β-catenin axis [2]. In DNA virus infection, mice with inactivated Kat5 exhibited lower levels of serum cytokines, higher viral titers, and more susceptibility to DNA-virus-induced death, indicating that KAT5-mediated cGAS acetylation is important for the innate immune response [4]. In anaplastic thyroid cancer (ATC), KAT5 promoted invasion and metastasis through C-MYC stabilization, and its inhibitor NU9056 suppressed ATC progression through the c-Myc/miR-202 pathway [5,6]. Also, KAT5 deficiency in myeloid cells and pharmacological inhibition of KAT5 enzymatic activity reduced activation of the NLRP3 inflammasome both in vitro and in vivo [7].

In conclusion, KAT5 is essential in multiple biological processes. Its role in diseases like MIRI, response to DNA virus infection, and ATC progression has been revealed through model-based research, especially KO/CKO mouse models. These studies help understand disease mechanisms and may provide potential therapeutic targets.