Klf6, a member of the Krüppel-like factors (KLFs) family of C2/H2 zinc finger DNA-binding proteins, plays crucial roles in multiple biological processes such as proliferation, metabolism, inflammation, and injury responses [1,2]. It is involved in various signaling pathways, like the mTOR/ULK1 pathway [1], and its dysregulation is associated with diseases including cancer, inflammation-associated diseases, and cardiovascular diseases [2]. Genetic models, especially knockout (KO) mouse models, are valuable for studying Klf6's functions.

In a mouse model of hepatic ischemia-reperfusion (I/R) injury, Klf6 deficiency exacerbated liver damage, cell apoptosis, and inflammatory responses, while overexpression had the opposite effects [1]. In myocardial I/R injury models, Klf6 knockdown restrained cell viability loss, improved myocardial injury, and inhibited ferroptosis [3]. In a male murine model of diabetic kidney disease (DKD), podocyte-specific induction of human Klf6 attenuated podocyte loss, proximal tubule (PT) dysfunction, and interstitial fibrosis [4]. In thymic epithelial cells (TEC), Klf6 deficiency led to a hypoplastic thymus, affecting TEC development and T cell selection, and resulting in autoimmunity [5]. In β-cells, inactivation of Klf6 blunted their proliferation induced by insulin resistance [6].

In conclusion, Klf6 is essential in maintaining normal physiological functions. Its dysregulation contributes to various disease conditions, as revealed by KO mouse models in areas such as liver I/R injury, myocardial I/R injury, DKD, thymus development, and β-cell adaptation to insulin resistance. These findings provide potential therapeutic targets for related diseases.