Klf2, also known as kruppel-like factor 2 (lung), is a member of the zinc finger transcription factor family. It critically regulates various biological processes such as embryonic lung development, endothelial cell function, and immune cell quiescence [4,6]. Klf2 is involved in multiple pathways, including those related to autophagy, immune cell differentiation, and inflammation regulation [1,4,6]. Genetic models, especially KO/CKO mouse models, have been valuable in studying Klf2's functions.

In a KO mouse model of acute LCMV infection, knockout of Klf2 led to aberrant differentiation to exhausted-like CD8 T cells, indicating Klf2 is required to maintain effector CD8 T cell lineage fidelity and suppress the exhaustion program [2]. In a mouse model of angiotensin II-induced non-ischemic cardiac dysfunction, Klf2 regulated neutrophil activation and thrombosis in the pathogenesis and progression of heart failure. Leukocytes from heart failure models showed reduced Klf2 mRNA expression, and chronic angiotensin II infusion activated a neutrophil KLF2/NETosis pathway leading to myocardial pathological changes [3]. In a mouse model of pulmonary hypertension, METTL3-mediated m6A modification of Klf2 was crucial for the endothelial-to-mesenchymal transition (EndMT) process. Endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH, while Klf2 overexpression mitigated EndMT [5].

In conclusion, Klf2 plays essential roles in immune cell function, autophagy, and cardiovascular and pulmonary vascular regulation. Model-based research, particularly KO/CKO mouse models, has revealed its significance in diseases such as heart failure, acute viral infections, and pulmonary hypertension, providing insights into disease mechanisms and potential therapeutic targets.