KLF14 is a zinc finger-containing transcription factor that functions as a metabolic and immune regulator with broad disease relevance. As a sequence-specific DNA-binding protein, KLF14 localizes to the nucleus and regulates transcription via RNA polymerase II 1. Functionally, KLF14 serves as a key metabolic transregulator with monoallelic maternal expression, primarily affecting adipose tissue gene expression and lipid metabolism 2. In sepsis, KLF14 protects against mortality by inhibiting hexokinase 2 (HK2) transcription, thereby reducing macrophage glycolysis and inflammatory cytokine secretion 1. KLF14 expression is upregulated in septic patients, and pharmacological activation confers sepsis protection in mice 1. Regarding metabolic disease, KLF14 variants associate with metabolic syndrome components including lipid profiles, insulin resistance, and blood pressure, predominantly in female and obese populations 2. The risk allele G of rs972283 increases type 2 diabetes risk globally 3. Epigenetically, KLF14 promoter hypermethylation associates with metabolically unhealthy phenotypes in an age- and sex-dependent manner 2. In cancer, KLF14 acts as a tumor suppressor. It promotes ferroptosis in cervical cancer by directly downregulating GPX4 through promoter binding 4, and inhibits breast cancer invasion by activating SOCS3 to block RhoA/Rock/STAT3 signaling and M2 macrophage polarization 5.