As global population aging intensifies, the rising incidence of neurodegenerative diseases poses a significant public health challenge. TREM2 (triggering receptor expressed on myeloid cells 2), an immune regulatory receptor specifically expressed in microglia, plays a dual role in neurodegenerative diseases by modulating phagocytosis, inflammatory responses, and cell metabolism. TREM2 can recognize damaged neurons and pathological proteins, such as β-amyloid. It then activates downstream signaling pathways like PI3K/Akt, driving microglia to an anti-inflammatory phenotype. This process clears toxic substances and maintains neuronal metabolic homeostasis. However, TREM2 gene mutations can lead to abnormal protein function, substantially increasing Alzheimer’s disease risk. This paper comprehensively reviews TREM2’s role in various neurodegenerative diseases, particularly in Alzheimer’s disease, aiming to underpin the development of TREM2-based therapies with theoretical evidence and novel insights.