TREM2 is intracellularly coupled to the adapter protein DAP12 (see for review: Linnartz et al., 2010), and interestingly, loss of function mutations of either TREM2 or DAP12 lead to a rare chronic neurodegenerative disease known as Nasu–Hakola or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), an inherited autosomal recessive human disease characterized by early onset presenile dementia (Colonna, 2003). Here, TYROBP is linked to Nasu-Hakola disease.