KLF5 is a sequence-specific DNA-binding transcription factor that recognizes GC box promoter elements and activates target gene transcription via RNA polymerase II 1. KLF5 functions as a critical regulator in multiple disease pathways. In diabetic kidney disease, lactate-induced histone H3K14 lactylation increases KLF5 expression, which then binds the CDH1 promoter to suppress E-cadherin transcription, accelerating epithelial-mesenchymal transition (EMT) and renal fibrosis; KLF5 knockdown attenuates disease progression 1. In diabetic cardiomyopathy, FOXO1 directly binds the KLF5 promoter to increase its expression, leading KLF5 to activate NADPH oxidase 4 (NOX4), which generates oxidative stress and induces ceramide accumulation and cardiac dysfunction; KLF5 inhibition reverses these effects 2. In cancer immunotherapy, KLF5 promotes immunosuppression by binding the COX2 promoter and increasing prostaglandin E2 production, which inhibits CD8+ T cell infiltration; KLF5 inhibition synergizes with anti-PD1 therapy 3. In ovarian cancer, super-enhancer-driven KLF5 forms transcriptional complexes with EHF and ELF3 to enhance RAD51 expression, promoting DNA repair and PARP inhibitor resistance 4. Additionally, KLF5 participates in pulmonary vascular remodeling via NOTCH3 activation 5, gastric intestinal metaplasia through STAT3-dependent pathways 6, and esophageal squamous cell carcinoma progression as part of core regulatory circuitry 7. These diverse functions establish KLF5 as a pleiotropic oncogenic transcription factor with therapeutic potential across multiple disease contexts.