Krüppel-like factor (KLF) family members share a three C2H2 zinc finger DNA binding domain, and are involved in cell proliferation and differentiation control in normal as in pathological situations. KLFs can be deregulated in multiple cancers either by loss of heterozygosity (LOH), somatic mutation or transcriptional silencing by promoter hypermethylation.

KLF family member proteins play a critical role in the growth and metastasis of numerous tumor types, at least in part by regulating the expression of cell cycle genes. Globally, KLF4 and KLF6 are considered as tumor suppressor gene, whereas KLF5 promotes cell proliferation. Family members have different transcriptional properties and can modulate each other's activity by a variety of mechanisms. Since cells can express multiple KLFs, KLF transcription factors build likely a transcriptional network to control cell proliferation. Effects of changes in KLF factors are context-dependent and can appear contradictory, considering differences in the expression profile of family members in various cells. Last, KLF variants may antagonize the function of wild type proteins.