Abstract
The Krüppel-like factors (KLFs) are a family of transcriptional regulators that play crucial roles in regulating diverse cellular processes including development, proliferation, differentiation, metabolism, and carcinogenesis across various tissues. KLFs play pivotal roles in gastrointestinal pathologies, and exhibit tissue- and cell-type-specific expression patterns throughout the gastrointestinal tract. During gastrointestinal (GI) development, KLFs orchestrate the transition from embryonic to adult gene programming, with specific family members being essential for proper organogenesis and tissue formation. KLFs also function as context-dependent modulators of GI homeostasis, inflammation, and carcinogenesis in adult tissues and interact with major signaling pathways such as PI3K/AKT, NF-κB, Wnt, Notch, MAPK, and TGF-β. This review comprehensively examines the roles of KLFs in GI health and disease, focusing on their expression patterns, regulatory mechanisms, function in normal homeostasis, and therapeutic implications for gastrointestinal disorders.