TCF7L2 (transcription factor 7 like 2) is a key transcription factor that functions as both a transcriptional activator and repressor in the canonical Wnt signaling pathway 1. The protein acts as a repressor in the absence of β-catenin (CTNNB1) and as an activator in its presence, modulating expression of target genes including MYC by binding to specific DNA sequences 2. TCF7L2 plays critical roles in metabolic regulation, particularly glucose homeostasis and amino acid metabolism, with liver-specific deletion disrupting hepatic zonation and glutamine metabolism 3. The gene harbors the strongest genetic association with type 2 diabetes risk identified to date, with variants consistently replicated across diverse populations 1. Beyond diabetes, TCF7L2 contributes to cancer biology, promoting anoikis resistance and metastasis in gastric cancer through transcriptional activation of PLAUR 4. Meta-analyses have revealed significant associations between TCF7L2 polymorphisms and increased susceptibility to breast, prostate, and colon cancers 56. In colorectal cancer, NOTCH2 directly activates TCF7L2 transcription, which then regulates Wnt target genes including MYC, JUN, and CCND1/2 2. The gene also shows associations with diabetic retinopathy risk in certain populations 7.