MSR1 (macrophage scavenger receptor 1, also known as CD204) is a membrane glycoprotein expressed primarily on macrophages that mediates endocytosis of modified lipoproteins and diverse macromolecules. It binds and internalizes acetylated and oxidized low-density lipoproteins, though isoform III does not internalize acetylated LDL. MSR1 plays a central role in atherosclerosis through cholesterol deposition in arterial walls and foam cell formation. Beyond lipid metabolism, MSR1 exhibits pleiotropic immune and pathogen-recognition functions. It mediates non-opsonic phagocytosis of the opportunistic fungus Cryptococcus neoformans through crosstalk with TLR4 1 and participates in myelin debris clearance by microglia across Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia 2. In non-alcoholic fatty liver disease, MSR1 expression correlates with hepatic steatosis and inflammation; mice lacking MSR1 show protection against diet-induced metabolic dysfunction and foamy macrophage formation, with MSR1 triggering pro-inflammatory signaling via the JNK pathway 3. MSR1 is also upregulated in tumor-associated macrophages during monocyte-to-M2 differentiation in lung cancer 4. Genetic variation in MSR1 affects disease risk. Copy number variants of MSR1 repeats at the KLK14 locus associate with breast and prostate cancer susceptibility 5, while rare and common MSR1 variants confer moderate risk in prostate cancer, particularly in black men 6. MSR1 mutations have been identified in hereditary gastric cancer families lacking CDH1 mutations 7. Monoclonal antibodies targeting MSR1 show promise in preclinical models of fatty liver disease.