CDH6 (cadherin 6) is a calcium-dependent cell adhesion protein that plays critical roles in both normal tissue development and cancer progression 1. In normal physiology, CDH6 functions in epithelial repair, where its dynamic expression determines regeneration outcomes - cells that silence CDH6 after injury heal without fibrosis, while those maintaining CDH6 expression develop a reprogrammed state that drives fibrosis through WNT signaling 1. CDH6 is overexpressed in multiple cancer types including ovarian, renal, and osteosarcoma, where it promotes metastatic behavior 23. Mechanistically, CDH6 enhances cancer cell migration and invasion through interaction with integrin αIIbβ3 via its RGD motif, which subsequently activates α2β1 integrin and downstream SRC, FAK, AKT, and ERK signaling pathways 3. CDH6 also promotes mitochondrial fission and is regulated by transcription factors like GLI2 4. In rheumatoid arthritis, CDH6 expression is elevated in fibroblast-like synoviocytes, promoting their aggressive behavior 5. Clinically, CDH6's limited expression in normal adult tissues but high expression in tumors makes it an attractive therapeutic target, with multiple antibody-drug conjugates showing promising antitumor activity in preclinical models 678.