KLF4 is a zinc finger transcription factor that functions as a multifunctional regulator of cell fate and inflammatory responses 1. It binds the 5'-CACCC-3' core sequence and can act as both transcriptional activator and repressor, with particular importance in maintaining stem cell pluripotency and preventing differentiation 2. KLF4 is one of four factors (OSKM) used to reprogram differentiated cells into induced pluripotent stem cells, demonstrating its central role in cell fate determination 2. In epithelial biology, KLF4 inhibition promotes keratinocyte precursor expansion and self-renewal while preserving immaturity, suggesting therapeutic potential for skin regeneration 3. KLF4 also functions as a tumor suppressor in lung cancer through the USP10-KLF4-TIMP3 axis, where KLF4 transcriptionally activates the tumor suppressor TIMP3 4. Regarding inflammation, KLF4 plays a pivotal dual role—it regulates immune response genes including IL1RL1, CD274, and CD44 in allergic rhinitis 5, and serves as a key checkpoint in alveolar macrophages, where phosphatase PHLPP1 suppresses KLF4 expression to prevent pulmonary fibrosis 6. KLF4 emerges as both a critical regulator of immune cell differentiation and a promising therapeutic target for inflammatory diseases 7. Additionally, KLF4 functions as a DNA methylation reader that activates genes through mCpG-dependent chr9 remodeling 8.