SCARB2 (scavenger receptor class B member 2), also known as LIMP-2, is a lysosomal integral membrane protein with diverse cellular functions. Functionally, SCARB2 acts as a lysosomal cholesterol transporter, binding and shuttling cholesterol across the transglycocalyx tunnel within lysosomes alongside NPC1 1. Additionally, SCARB2 serves as a cellular receptor for enteroviruses, including enterovirus 71 and Coxsackievirus A16, which cause hand, foot, and mouth disease 2. Beyond viral infection, SCARB2 is a cargo receptor involved in lipophagy—selective autophagy of lipid droplets—and mediates cholesterol efflux in macrophage foam cells 3. Mechanistically, SCARB2 regulates lipid and cholesterol metabolism through multiple pathways. In hepatocellular carcinoma, SCARB2 binding to MYC promotes its acetylation and transcriptional activity, driving cancer stem cell properties 4. In obesity-related breast cancer, glutathione directly binds SCARB2 at lysosomes, recruiting mTORC1 through ARF1 to activate mTOR signaling 5. SCARB2 knockdown in adipocytes alters lipid composition, reducing triacylglycerols while modulating phosphatidylcholine and ceramide levels 6. Clinically, SCARB2 variants (rs8475, rs6812193) associate with Parkinson's disease risk, particularly sporadic PD, though they do not modify disease onset 7. SCARB2 expression is reduced in GBA-associated parkinsonism 7. SCARB2 is also implicated in progressive myoclonic epilepsy type 4. These associations suggest SCARB2 dysfunction impairs lysosomal function and neuronal homeostasis.