Klf15, or Krüppel-like factor 15, is a transcription factor that plays crucial roles in multiple biological processes. It is involved in regulating metabolism, oxidative stress response, and maintaining cell phenotypes. Klf15 is associated with various signaling pathways, such as those related to muscle atrophy, cardiac function, and endobiotic/xenobiotic metabolism, highlighting its overall biological importance. Genetic models, especially KO/CKO mouse models, have been instrumental in studying its functions [3,5,6,7,8,9].

In muscle, KLF15 deficiency in skeletal muscle protects mice from immobility-induced muscle atrophy, suggesting its role in the Piezo1/KLF15/IL-6 axis that mediates this process [1]. In the heart, cardiomyocyte-specific overexpression of the ubiquitin E3 ligase WWP1, which targets KLF15 for degradation, exacerbates cardiac ischemic injury, while WWP1 inhibition mitigates it, indicating KLF15's protective role against such injury [2]. In pancreatic cancer, KLF15 suppresses the stemness of pancreatic ductal adenocarcinoma cells by promoting the degradation of Nanog [4]. In the kidneys, SIRT7 mitigates renal ferroptosis, fibrosis, and injury in hypertensive mice by facilitating the KLF15/Nrf2 signaling [5]. In the liver, knockout of hepatocyte KLF15 induces the expression of Cyp3a11 and attenuates rifampicin-induced hepatotoxicity [6]. In vascular smooth muscle cells, Klf15KO mice are more susceptible to thoracic aortic dissection, and KLF15 deficiency reduces VSMC contractility [7]. In cardiomyocytes, acute KLF15 deficiency in neonatal rat ventricular myocytes leads to defective ROS clearance and exaggerated cell death due to reduced NAMPT and NAD+ levels [9]. In triple-negative breast cancer, exogenous expression of KLF15 suppresses cell growth and metastasis by downregulating CCL2 and CCL7 [10].

In conclusion, Klf15 plays essential roles in metabolism, oxidative stress response, and maintaining cell phenotypes across various tissues. Model-based research, particularly using Klf15 KO/CKO mouse models, has revealed its significance in diseases such as muscle atrophy, cardiac ischemic injury, pancreatic cancer, hypertensive renal injury, liver injury, thoracic aortic dissection, and triple-negative breast cancer. These findings enhance our understanding of the biological functions of Klf15 and provide potential therapeutic targets for these diseases.