Work

KLF15 as a Metabolic Gatekeeper Linking Drug Metabolism, Toxicity, and Precision Therapeutics

Year: 2026

Type: article

Abstract: ABSTRACT Krüppel‐like factor 15 (KLF15) is emerging as a metabolic‐state‐sensitive regulator of hepatic endobiotic and xenobiotic metabolism. The strongest causal evidence comes from mouse liver, where KLF15 directly and indirectly controls phase I–III enzymes and transporters, thereby modulating the detoxification and disposition of acetaminophen, rifampicin, and cyclosporine A. Evidence from the heart, vasculature, skeletal muscle, kidney, and tumor models establishes broader roles in metabolic adaptation and stress responses, but direct effects on extrahepatic drug disposition remain largely untested. In this Perspective, we review the established KLF15‐drug metabolism relationship from mouse studies and inferential evidence from clinical data, as well as mechanistically plausible extrahepatic extensions. Furthermore, we discuss the translational potential of KLF15 as a biomarker or therapeutic target that may advance precision medicine.

Source: iNew Medicine

DOI: 10.1002/inm3.70096

Authors: Shilin Li, Xue Li, Zhengding Su, Shuxin Han

Institutions: Dazhou Central Hospital, Xinjiang University, Central People's Hospital of Zhanjiang

Language: English

Topic: Kruppel-like factors research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Natural Science Foundation of China