CDH1 (E-cadherin) forms a homotypic trans-complex with CDH1 molecules presented on the plasma membrane of a neighbouring cell, where two CDH1 molecules interact through their extracellular domains in a calcium (Ca2+)-dependent, and catenin-dependent manner (Chitaev and Troyanovski 1998). Based on a structural study using the extracellular domain of the mouse CDH1, it was determined that twelve Ca2+ ions per CDH1 molecule were needed for homotypic dimerization (Nagar et al. 1996). Another study with the mouse CDH1 reported that nine Ca2+ ions per CDH1 molecule were sufficient for homotypic dimerization (Koch et al. 1997). Using super-resolution microscopy techniques it was found that loosely organized cis-clusters of approximately five CDH1 molecules serve as the precursors of trans-ligated adhesive clusters, consisting of homotypic trans-dimers, that make up the adherens junction (Wu et al. 2015; reviewed in Zhang et al. 2023). CDH1 clusters in both interacting cells are surrounded by the cytosolic F-actin meshwork, but the F-actin meshwork is not necessary for the establishment of homotypic trans-interactions (Wu et al. 2015).