Cadherinâ4, also known as RâCadherin, is a 120â140 kDa type I transmembrane protein belonging to the Cadherin superfamily of calciumâdependent adhesion molecules. Cadherinâ4 is expressed in epithelial cells, vascular smooth muscle cells, glial and neuronal cells, pancreatic beta âcells, thyroid follicular cells, and bone marrow Linâ hematopoietic stem cells. It interacts in cis to form homodimers as well as heterodimers with NâCadherin which function as adhesion multimers in trans-configuration. It is downregulated in invasive breast cancer but upregulated in rhabdomyosarcoma and has been shown to exert both positive and negative effects on cell migration and tumor cell invasiveness. Cadherinâ4 is involved in a variety of homing processes including guidance of the optic nerve and pioneer axons in early brain development, branching and guidance of the retinal vasculature, and targeting of hematopoietic stem cells to sites of ischemia. Cadherinâ4 additionally binds to KLRG1, an inhibitory receptor expressed on NK cells.