NKG2D: A versatile player in the immune system

•NKG2D can induce direct killing of target cells expressing its ligands, which are stress-induced.•NKG2D is expressed in hematopoietic precursors and affects NK cell and B1a cell development.•NKG2D deficiency results in permanent hyper-reactivity of NK cells and hypo-responsiveness of B1a cells.•On CD8 T cells, NKG2D mediates effector cell differentiation and memory formation during priming.•The role of NKG2D in a given subset depends on the adaptors Dap10 and Dap12 and the presence of unknown co-factors.