Klf5, also known as Krüppel-like Factor 5, is a transcription factor belonging to the KLF family. It regulates the expression of numerous target genes and is involved in diverse cellular functions such as stemness, proliferation, apoptosis, autophagy, and migration [2]. It participates in multiple signaling pathways, and its expression level and activity are affected by various transcriptional modulation and post-translational modifications. Transgenic mouse models have been crucial in revealing its physiological and pathological functions [2].

In cancer research, Klf5 inactivation decelerated basal-like breast tumor growth in a CD8+ T-cell-dependent manner. KLF5 binds to the COX2 gene promoter, promoting COX2 transcription. Thus, KLF5 deficiency decreases prostaglandin E2 (PGE2) release from tumor cells, increasing the number and functionality of intratumoral antitumor T cells, and synergizing with anti-PD1 therapy [1]. In ovarian cancer, SEs-driven KLF5 promotes tumor progression and PARPi resistance by forming a transcriptional complex with EHF and ELF3 to enhance RAD51 transcription, strengthening the homologous recombination repair (HRR) pathway [5]. In PTEN-deficient prostate cancer, interruption of KLF5 acetylation reprograms cancer-associated fibroblasts, enhancing FGF receptor 1 (FGFR1) signaling and promoting tumor growth [6].

In conclusion, Klf5 plays a significant role in cancer development and progression as revealed through mouse model-based research. In breast, ovarian, and prostate cancers, its inactivation or modulation can have potential therapeutic implications. Also, in non-cancer diseases like diabetic kidney disease and diabetic cardiomyopathy, Klf5 is involved in disease-related processes such as epithelial-mesenchymal transition and oxidative stress respectively [3,4]. The study of Klf5 using gene knockout or conditional knockout mouse models provides insights into its function in disease mechanisms, offering potential therapeutic targets.