Review of the biochemical properties of the different NKG2D-ligands supports the idea that evolution of these molecules was significantly driven as a result of selective pressure exerted by a range of stress signals and pathogen infections: if an insult resulted in blockade of a particular cellular pathway, obstructing the expression of an NKG2D-ligand, the existence of a different ligand that could follow an alternative route to make the cell visible to the immune system would be an advantage. The gene discussed is KLRK1; the disease is infection.