TREM2 and bone disorder: After the discovery of the TREM2/DAP12 complex in the immune system, both molecules were sequentially identified as causative genes for Nasu-Hakola disease [also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL)], which is characterized by presenile dementia with bone cysts (Paloneva et al., 2000, 2002).