TFF3 binding to LINGO2 reverses tonic inhibition of epidermal growth factor receptor (EGFR) by LINGO2, resulting in heightened EGFR activation.14 Other signal transduction data concerning TFF3 remain elusive and mainly result from migration and apoptotic assays, without providing target receptors or mechanistic details.3 This lack of knowledge hampers attempts to elucidate the molecular mechanisms underlying the functional role of TFF3 in mucosal restitution and CRC development and indicates that TFF3 may work differently from the canonical receptor-mediated activation of signaling. The gene discussed is LINGO2; the disease is colorectal carcinoma.