TOLLIP and Nasu-Hakola disease: 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).