Very low-density lipoprotein receptor (VLDLR)

The Very low-density lipoprotein receptor (VLDLR) is a multifunctional endocytic receptor of the low-density lipoprotein receptor family, structurally homologous to LDL receptor but with broader tissue expression—particularly in adipose tissue, muscle, heart, and brain (excluding hepatocytes)[2][4][8]. VLDLR binds and mediates the uptake of apolipoprotein E-containing lipoproteins (including VLDL and chylomicron remnants), thus regulating triglyceride-rich lipoprotein clearance, lipid storage, and cholesterol homeostasis outside the liver[2][4][8]. Uniquely, VLDLR also serves as a receptor for reelin in the central nervous system, coordinating neuronal migration and brain development[4][6]. Mutations or deficiency in VLDLR cause rare human disorders with cerebellar hypoplasia and motor defects, while overexpression or dysregulation may contribute to atherosclerosis and metabolic syndrome. Therapeutically, VLDLR is indirectly targeted through nuclear receptor (PPAR-γ) modulation and possibly by PCSK9 regulation, rather than by direct agonists or antagonists[2][4]. There is growing interest in VLDLR as a drug target in metabolic and neurological diseases but direct pharmacological agents have not yet advanced to clinic.

Other names

Very low density lipoprotein receptorVLDLRVLDL receptorVLDL-RCARMQ1CAMRQ1CHRMQ1VLDLRCH

Indirect modulation via PPAR-γ agonism (enhanced VLDLR expression leads to increased fat deposition and VLDL/TG clearance). Regulatory effects by PCSK9 (post-translational degradation of VLDLR affects cholesterol uptake). No approved small-molecule or biologic inhibitors/agonists directly targeting VLDLR in current clinical use.