The Krüppel-like factor (KLF) family of transcription factors plays a crucial role in regulating various biological processes, including proliferation, differentiation, growth, development, survival, and responses to external stress. Seventeen mammalian KLFs have been identified, and extensive research has been conducted to understand their basic biology and contributions to human diseases. KLF proteins are involved in the development and homeostasis of numerous organ systems, including the cardiovascular, digestive, respiratory, hematological, and immune systems. They are also implicated in disorders such as obesity, cardiovascular disease, cancer, and inflammatory conditions. Additionally, KLFs are essential in reprogramming somatic cells into induced pluripotent stem (iPS) cells and maintaining the pluripotent state of embryonic stem cells. KLF proteins share common mechanisms of regulation, recruiting transcriptional regulatory proteins such as co-activators and co-repressors, as well as chromatin remodeling proteins. They exhibit conserved zinc finger domains that allow them to bind GC-rich sites in promoter and enhancer regions of genes they regulate. KLFs can be divided into three groups based on their functional characteristics: Group 1 serves as transcriptional repressors, Group 2 functions predominantly as transcriptional activators, and Group 3 has repressor activity through interaction with the common transcriptional co-repressor Sin3A. Post-translational modifications, such as acetylation, phosphorylation, ubiquitination, and sumoylation, refine the transcriptional activity of KLF family members. These modifications are regulated by signaling pathways and affect the association of histone acetyltransferases (HATs) and histone deacetylases (HDACs) with KLF proteins. KLFs regulate proliferation, differentiation, and apoptosis in various cell types. For example, KLF5 promotes proliferation by accelerating cells through the cell cycle, while KLF4 inhibits cell cycle progression and induces cell cycle arrest following DNA damage. KLFs also play critical roles in the development and pathobiology of the cardiovascular system, endothelial biology, and vascular smooth muscle biology. In the cardiovascular system, KLF13 is essential for cardiac development, while KLF2 is important for vascular endothelial function and response to injury. In endothelial cells, KLFs regulate anti-inflammatory and anti-thrombotic functions, while in vascular smooth muscle cells, KLF5 induces proliferation and contributes to vascular remodeling. Overall, the study of KLF proteins continues to reveal new biological and pathobiological roles, highlighting their importance in various physiological and pathological processes.The Krüppel-like factor (KLF) family of transcription factors plays a crucial role in regulating various biological processes, including proliferation, differentiation, growth, development, survival, and responses to external stress. Seventeen mammalian KLFs have been identified, and extensive research has been conducted to understand their basic biology and contributions to human diseases. KLF proteins are involved in the development and homeostasis of numerous organ systems, including the cardiovascular, digestive, respiratory, hematological, and immune systems. They are also implicated in disorders such as obesity, cardiovascular disease, cancer, and inflammatory conditions. Additionally, KLFs are essential in reprogramming somatic cells into induced pluripotent stem (iPS) cells and maintaining the pluripotent state of embryonic stem cells. KLF proteins share common mechanisms of regulation, recruiting transcriptional regulatory proteins such as co-activators and co-repressors, as well as chromatin remodeling proteins. They exhibit conserved zinc finger domains that allow them to bind GC-rich sites in promoter and enhancer regions of genes they regulate. KLFs can be divided into three groups based on their functional characteristics: Group 1 serves as transcriptional repressors, Group 2 functions predominantly as transcriptional activators, and Group 3 has repressor activity through interaction with the common transcriptional co-repressor Sin3A. Post-translational modifications, such as acetylation, phosphorylation, ubiquitination, and sumoylation, refine the transcriptional activity of KLF family members. These modifications are regulated by signaling pathways and affect the association of histone acetyltransferases (HATs) and histone deacetylases (HDACs) with KLF proteins. KLFs regulate proliferation, differentiation, and apoptosis in various cell types. For example, KLF5 promotes proliferation by accelerating cells through the cell cycle, while KLF4 inhibits cell cycle progression and induces cell cycle arrest following DNA damage. KLFs also play critical roles in the development and pathobiology of the cardiovascular system, endothelial biology, and vascular smooth muscle biology. In the cardiovascular system, KLF13 is essential for cardiac development, while KLF2 is important for vascular endothelial function and response to injury. In endothelial cells, KLFs regulate anti-inflammatory and anti-thrombotic functions, while in vascular smooth muscle cells, KLF5 induces proliferation and contributes to vascular remodeling. Overall, the study of KLF proteins continues to reveal new biological and pathobiological roles, highlighting their importance in various physiological and pathological processes.