Triggering receptor expressed on myeloid cells 2 (TREM2) is a key transmembrane immune receptor that is specifically highly expressed in myeloid cells, particularly macrophages, within atherosclerosis (AS) plaques. Advances in single-cell sequencing technology have clearly defined TREM2-high macrophages as a distinct subpopulation known as lipid-associated macrophages. TREM2 exhibits stage-specific bidirectional regulatory effects during the progression of AS. In the early stage of the disease, TREM2 promotes cholesterol uptake by upregulating the scavenger receptor CD36, thereby accelerating foam cell formation and lesion expansion. In the advanced stage, however, its protective effects become prominent: TREM2 enhances macrophage survival, drives reverse cholesterol transport, and improves efferocytosis efficiency, thereby effectively inhibiting necrotic core expansion and maintaining plaque stability. At the molecular level, the TREM2-DAP12 complex upregulates CD36-mediated lipid uptake through the p38 mitogen-activated protein kinase/peroxisome proliferator-activated receptor gamma (PPARγ) axis, whereas deficiency of liver X receptor (LXR) can weaken its protective effects. Mitochondrial reactive oxygen species (mtROS) drive the transition of macrophages toward a pro-inflammatory foam cell phenotype through signal transducer and activator of transcription 5 (STAT5). In addition, ferroptosis-related mitochondrial dysfunction promotes the death of advanced foam macrophages and aggravates plaque instability. In terms of clinical translation, soluble TREM2 (sTREM2) levels are associated with the risk of coronary heart disease and adverse cardiovascular events, suggesting that sTREM2 may serve as a potential biomarker reflecting plaque inflammation and cellular injury and may provide incremental predictive value beyond high-sensitivity C-reactive protein. TREM2 agonists, such as AL002a, can reprogram foam macrophages and enhance efferocytosis and necrotic core clearance, thereby improving plaque stability and showing potential for precision intervention. In summary, TREM2 shows a "double-edged sword" role at different stages of AS, and precise stage-specific modulation of TREM2 may represent a new direction for immunotherapy in AS. 触发髓样细胞表达的受体2(triggering receptor expressed on myeloid cells 2，TREM2)是一种关键的跨膜免疫受体，在动脉粥样硬化(atherosclerosis，AS)斑块髓系细胞(尤其是巨噬细胞)中呈特异性高表达。单细胞测序技术的演进已明确将TREM2高表达巨噬细胞界定为脂质相关巨噬细胞这一独特亚群。TREM2在AS演变过程中表现出阶段特异性的双向调控作用:在疾病早期，TREM2通过上调清道夫受体CD36促进胆固醇摄取，加速泡沫细胞形成与病变扩张;进入晚期，其保护效应凸显，通过增强巨噬细胞存活、驱动胆固醇逆转运及提升胞葬作用效率，有效抑制坏死核心扩大并维持斑块稳定。在分子机制层面，TREM2-DNAX激活蛋白12(DNAX-activating protein of 12 kD，DAP12)复合体经p38丝裂原活化蛋白激酶/过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma，PPARγ)轴上调CD36介导脂质摄取，而肝X受体(liver X receptor，LXR)缺陷可削弱其保护作用。线粒体活性氧(mitochondrial reactive oxygen species，mtROS)经信号转导及转录激活因子5(signal transducer and activator of transcription 5，STAT5)驱动巨噬细胞向促炎泡沫表型转化;铁死亡相关的线粒体功能障碍则促进晚期泡沫巨噬细胞死亡，加重斑块失稳。在临床转化方面，可溶性TREM2(soluble TREM2，sTREM2)水平与冠心病及心血管不良事件风险相关，提示其可作为反映斑块炎症与细胞损伤的潜在生物标志物，并可能提供超越高敏C反应蛋白的增量预测价值;TREM2激动剂(如AL002a)可重编程泡沫巨噬细胞、增强胞葬与坏死核心清除，从而提升斑块稳定性，展现出精准干预潜力。综上，TREM2在AS不同阶段呈现“双刃剑”特征，针对其阶段特异性的精准调控有望成为AS免疫治疗的新方向。.