VLDLR
VLDLR (very-low-density lipoprotein receptor) is a member of the LDL receptor family that mediates the endocytosis of apolipoprotein E-containing triglyceride-rich lipoproteins and contributes to peripheral lipid metabolism and cellular lipid uptake[1]. Mechanistically, VLDLR also functions as a key receptor in the Reelin signaling pathway, where Reelin binding triggers intracellular signaling events that regulate neuronal migration, cortical layering, and cerebellar development during embryogenesis[2][3]. Through these signaling activities, VLDLR links lipid receptor biology with neurodevelopmental processes and synaptic function in the central nervous system[2][3]. In disease settings, loss-of-function mutations in VLDLR disrupt Reelin-dependent neuronal positioning and are associated with VLDLR-associated cerebellar hypoplasia and dysequilibrium syndrome, making VLDLR-deficient models valuable tools for studying brain development and neurodevelopmental disorders[2][4]. Compared with the closely related receptor ApoER2, VLDLR shares the ability to mediate Reelin signaling but exhibits distinct expression patterns and biological functions that contribute differently to neuronal development and adult neural physiology[3]. A notable feature of VLDLR is the presence of alternative splice isoforms, including VLDLR-I and VLDLR-II, which differ in the O-linked glycosylation domain and display distinct functional properties, highlighting isoform-specific regulation as an important consideration in mechanistic studies[5]. Therefore, VLDLR serves as a multifunctional receptor integrating lipid metabolism and Reelin-dependent signaling and remains an important target for experimental investigation of neurodevelopmental and metabolic pathways[1][2][3].
References:
- [1]. Takahashi S, et al. The very low-density lipoprotein (VLDL) receptor: characterization and functions as a peripheral lipoprotein receptor. J Atheroscler Thromb. 2004;11(4):200-8. [Content Brief]
- [2]. Vila M, et al. Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci. 2003 May;4(5):365-75. [Content Brief]
- [3]. Liu X, et al. Physical layer encryption scheme based on biological genetic variation mechanisms in CO-OFDM system. Opt Express. 2025 Oct 6;33(20):42528-42541. [Content Brief]
- [4]. Boycott KM, et al. Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet. 2005 Sep;77(3):477-83. [Content Brief]
- [5]. Chen Q, et al. Functional Differences of Very-Low-Density Lipoprotein Receptor Splice Variants in Regulating Wnt Signaling. Mol Cell Biol. 2016 Sep 26;36(20):2645-54. [Content Brief]
