LEF1 and TCF are members of the high mobility group (HMG) DNA-binding protein family of transcription factors that consists of the following: Lymphoid Enhancer Factor 1 (LEF1), T Cell Factor 1 (TCF1/TCF7), TCF3/TCF7L1, and TCF4/TCF7L2 . LEF1 and TCF1/TCF7 were originally identified as important factors that regulate early lymphoid development and act downstream in Wnt signaling. LEF1 and TCF bind to Wnt response elements to provide docking sites for β-catenin, which translocates to the nucleus to promote the transcription of target genes upon activation of Wnt signaling. LEF1 and TCF are dynamically expressed during development and aberrant activation of the Wnt signaling pathway is involved in many types of cancers, including colon cancer .TCF4/TCF7L2 is expressed widely during development. Gene targeting studies indicate that TCF4/TCF7L2 is required to maintain the crypt stem cells of the small intestine . TCF4/TCF7L2 has several splicing isoforms that are expressed differentially in tissues and during cancer progression . Studies also indicate that a variant of the TCF4/TCF7L2 gene confers an increased risk of type 2 diabetes .