E-cadherin heterophilically interacts with KLRG1 and α_E(CD103)β₇. E-cadherin contains an ectodomain composed of 5 extracellular cadherin (EC1-5) repeats, a transmembrane region, and a cytoplasmic tail. The latter can be further subdivided into a β-catenin binding domain (CBD) and a membrane proximal cytoplasmic/conserved domain (MPCD) important for p120-catenin binding. EPLIN was reported to link the E-cadherin/β-catenin/α-catenin complex to F-actin.⁶  The E-cadherin ectodomain has been shown to bind to the inhibitory ITIM-containing receptor KLRG1, which is expressed on subsets of CD4⁺ T cells, including regulatory T-cell subsets, subsets of CD8⁺ T cells in distinct differentiation stadia, and mature NK cells. KLRG1 triggering results in reduced NK cytotoxicity and reduced CD8⁺ T-cell proliferation, suggesting that E-cadherin⁺ APCs might have the capacity to dampen lymphocyte functions. In addition, the KLRG1–E-cadherin interaction leads to E-cadherin phosphorylation and downstream signaling, resulting in reduced inflammatory cytokine production by the E-cadherin expressing cell. E-cadherin also binds to the α_E(CD103)β₇ integrin, possibly mediating adhesive interactions with α_E(CD103)β₇⁺ cells, such as IELs and DETCs, regulatory T-cell subsets, CD8⁺ T-cell subsets, and DC subsets. On T cells, this interaction was shown to mediate retention in tissues, costimulation, and enhanced cytotoxic activity (for CD8⁺ T cells).