Msr1, also named CD204, is a key receptor mainly present on the surface of various macrophages. It plays significant roles in multiple pathophysiologic processes, including inflammation, innate and adaptive immunity, and lipid metabolism. It is involved in pathways like PI3K/AKT/GSK3β/β-catenin, JNK, and Mafb/Msr1/PI3K-Akt/NF-κB, and is crucial for processes such as efferocytosis, macrophage polarization, and lipid uptake [2].

In Msr1 knockout (KO) mouse models, delayed intramembranous ossification was observed compared to wild-type mice, suggesting that macrophage Msr1 promotes bone marrow stem cell (BMSC) osteogenic differentiation and M2-like polarization by activating the PI3K/AKT/GSK3β/β-catenin pathway [1]. Msr1-deficient mice were protected against diet-induced metabolic disorder in non-alcoholic fatty liver disease (NAFLD), showing fewer hepatic foamy macrophages, less hepatic inflammation, and improved dyslipidaemia and glucose tolerance [4]. Additionally, depletion of neutrophil leukocytes or ablation of Msr1 protected mice from tissue damage and the hyperinflammatory response in a model related to adult-onset Still's disease [3].

In conclusion, Msr1 is essential for macrophage-related functions and lipid-induced inflammation. KO mouse models have revealed its role in diseases such as fracture repair, NAFLD, and adult-onset Still's disease, highlighting its potential as a therapeutic target in these disease areas.