Emerging roles of KLF4 regulation of autophagy in different physiological and pathological processes.

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that exhibits both transcriptional activation and inhibition effects. It participates in the occurrence and development of various diseases by regulating processes such as cell cycle arrest, differentiation, and the maintenance of stem cell pluripotency. Autophagy, as a conserved lysosome dependent degradation pathway in eukaryotes, maintains cellular homeostasis by clearing abnormal proteins and damaged organelles. Its dysfunction is closely related to tumors, neurodegenerative diseases, metabolic disorders, and so on. Growing evidence indicates that KLF4 participates in multiple physiological and pathological processes through regulating autophagy, however, the underlying mechanisms are not fully understood. This article systematically reviewed the understanding of KLF4 and autophagy in recent years, critically synthesized the complex and context-dependent roles of KLF4-mediated autophagy regulation in different physiological and pathological processes, and analyzed the relevant molecular mechanisms, with an emphasis on identifying overarching regulatory patterns and functional consequences, hoping to provide theoretical basis for future in-depth research.