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In vitro experiments have revealed that CDH17 forms homophilic trans- and cis- complexes in a calcium-dependent manner44, 72, 87 89. A CDH17 inhibitory peptide, designed based on expected structural similarities to classical cadherins, interfered with homophilic trans adhesion in CACO2 cells forming epithelial layers and resulted in interstitial cleft widening72. Experiments also revealed that CDH17 is capable of forming heterophilic trans interactions with the classical cadherin CDH1, which is expressed in the same cell types as CDH1744. However, a structural basis for how CDH16 and CDH17 interact in cis and trans to mediate homophilic and heterophilic adhesion is not known.