The functional loss of triggering receptor expressed on myeloid cells-2 (TREM2) leads to a chronic neurodegenerative disease, named Nasu-Hakola disease. A murine in vitro study revealed that the absence of TREM2 expression on microglia impaired phagocytosis for tissue debris clearance and increased pro-inflammatory cytokine production; these are necessary to maintain the microenvironmental homeostasis of the central nervous system. On the other hand, the function of TREM2 is still unclear, especially in the fields of human pathology and morphology. In 2013, it was reported that non-synonymous variants of TREM2 were associated with Alzheimer's disease in Caucasians; however, supplementary studies in Asian populations, such as the Japanese, could not confirm this result. In this review, I discuss how TREM2 can contribute to neurodegenerative disease.