Rae-1 epsilon is a member of a family of cell-surface proteins that function as ligands for mouse NKG2D. Other family members are designated Rae-1 alpha, beta, gamma, and δ. Amino acid sequence identity within this family ranges from 88‑95%. The Rae-1 proteins are distantly related to MHC class I proteins, but they possess only the alpha 1 and alpha 2 Ig‑like domains, and they have no capacity to bind peptide or interact with beta 2-microglobulin. The genes encoding these proteins are not found within the Major Histocompatibility Complex on mouse chromosome 17, but rather map to mouse chromosome 10. The Rae-1 proteins are anchored to the membrane via a GPI‑linkage. The name of this family derives from the original identification of these proteins as the product of retinoic acid early inducible transcripts. Rae-1 expression is developmentally controlled. Transcripts were observed in the brain/head region of day 10‑14 embryos but disappeared by day 18. Rae-1 transcripts were detected in several transformed cell lines but are absent from most normal adult tissues. All Rae-1 family members bind to mouse NKG2D, an activating receptor expressed on NK cells and some T cell subsets, resulting in the activation of cytolytic activity and/or cytokine production by these effector cells. Ectopic expression of Rae-1 on mouse tumor cell lines resulted in the in vivo rejection of the tumors (1‑7).