TFF3 (trefoil factor 3) is a secreted peptide primarily involved in maintenance and repair of gastrointestinal epithelium, functioning as a motogen that promotes epithelial cell mobility during healing processes 1. In the intestine, TFF3 works through CD147 receptor binding to activate STAT3 signaling and induce PTGS2 expression, leading to prostaglandin E2 production that facilitates mucosal restitution 1. TFF3 is co-expressed with MUC2 in goblet cells and serves as a marker of goblet cell differentiation in colorectal tissue 2. Beyond the gastrointestinal tract, TFF3 is expressed in tracheobronchial airways 3 and widely distributed in the central nervous system, particularly in hypothalamic oxytocin-producing neurons and midbrain nuclei, where it modulates fear, depression, learning, and addiction-related processes 45. TFF3 expression is transcriptionally regulated by the Sp1 transcription factor 6. Clinically, elevated TFF3 in colorectal cancer predicts worse prognosis and promotes tumor progression through CD147-mediated signaling 1. Additionally, TFF3 associates with endometrial and breast cancers with adverse outcomes, though shows better prognosis in ovarian cancer 7. Cathelicidin-regulated TFF3 secretion from goblet cells is essential for mucosal defense against pathogens 8.