VLDLR: A Multifunctional receptor in diverse pathophysiological processes

The very low-density lipoprotein receptor (VLDLR), a member of the low-density lipoprotein receptor superfamily, mediates the endocytosis of very-low-density lipoproteins and participates in a wide range of physiological and pathological processes, including neurodevelopment, viral infection, and angiogenesis. Recent studies have shown that VLDLR facilitates alphavirus entry and exhibits a distinct spatiotemporal expression pattern in the liver. This review summarizes the structural features of VLDLR and systematically evaluates its multifaceted roles: mediating viral entry; promoting hepatic VLDL uptake to lower circulating lipid levels; transducing Reelin signaling for cortical and cerebellar lamination; suppressing pathological retinal angiogenesis; and modulating cancer progression. These insights provide a comprehensive overview of the versatile functions of VLDLR.