This review provides a comprehensive overview of the current evidence on the roles of TREM2+macrophages in regulating lipid metabolism and immune responses in MASH, with emphasis on the functions of TREM2+ macrophages in lipid handling and inflammation regulation, which could provide novel insights into the pathogenesis of MASH and inform targeted therapeutic strategies. The gene discussed is TREM2; the disease is metabolic dysfunction-associated steatohepatitis.