ULBP2 is a human ligand for the NKG2D receptor, together with at least ULBP1 and ULBP3. ULBPs activate multiple signaling pathways in primary NK cells, resulting in the production of cytokines and chemokines. Binding of ULBPs ligands to NKG2D induces calcium mobilization and activation of the JAK2, STAT5, ERK and PI3K kinase/Akt signal transduction pathway. The interaction with UL16 blocks the interaction with the NKG2D receptor, providing a mechanism by which CMV infected cells might escape the immune system UL16 also causes ULBP2 to be retained in the ER and cis-Golgi apparatus so that it does not reach the cell surface. ULBP2 is expressed in various types of cancer cell lines and in the fetus, but not in normal tissues.