Whilst TREM2 regulates phagolysosomal function, its effects on the deposition of misfolded protein in other models of proteinopathy are inconclusive and suggest that TREM2 and microglia likely influence neurodegenerative disease processes in proteinopathy through mechanisms beyond influencing misfolded protein deposition or clearance. This evidence concerns the gene TREM2 and proteostasis deficiencies.