This study investigates the effects of a loss of TREM2 on microglia function, particularly in response to neurodegenerative protein tau. Dissociation, aggregation and spread of tau amongst neurons in the brain has been linked to pathology in neurodegenerative disease such as Alzheimer’s Disease. Microglia play critical roles in the uptake and clearance of tau, amyloid-β, dead cells and other pathogens through phagocytosis. Microglial phagocytosis is mediated by cell surface receptors such as scavenger receptors like CD33 and TREM2. The R47H loss of function variant of TREM2 is a mutation found to increase the risk of AD three-fold. There are studies showing that microglia play a role in the clearance of amyloid-β plaques, and a knockdown of TREM2 impairs microglial phagocytosis of these plaques. However, the role that microglia, and specifically TREM2, plays in tau pathology is not well understood. In this study, using an induced pluripotent stem cell (iPSC)-derived microglia model, we aim to show that a knockdown of TREM2 perturbs phagocytosis relevant genes that may be involved in the internalization of tau as well as interrogate the direct effect TREM2 knockdown has on phagocytosis of tau.