Kruppel-like factor 5 (KLF5) belongs to a family of zinc-finger-containing transcription factors that are involved in regulating the expression of a wide range of genes, thereby affecting diverse cellular functions. The activities of KLF5 are regulated by multiple signaling pathways including Wnt, Ras, TGFbeta, Hippo, Notch, retinoic acid receptor, and hormone receptors. The expression of KLF5 is frequently abnormal in human cancers and the functions of KLF5 are context-dependent. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. Kruppel-like factor (KLF) 5, which initiates vascular smooth muscle cell (VSMC) proliferation, also participates in Angiotensin (Ang) II-induced vascular remodeling. Kruppel-like factor 5 (KLF5) is a key transcriptional regulator that is typically pro-proliferative in non-transformed epithelial cells but inhibits proliferation in transformed epithelial cells.