We report here the identification of a novel member of the low-density lipoprotein receptor(the LDL receptor) family through signal sequence trap screening of a mouse lymphocyte cDNA library.The protein was termed LDL receptor-related protein 9 (LRP9). LRP9 is a type I membrane proteinpredicted to contain 696 amino acids with a calculated molecular mass of 74 764 Da. The NH
2-terminalhalf of LRP9 contains two CUB domains separated by a single ligand-binding repeat. The second CUBdomain is followed by a cluster of three additional ligand-binding repeats and a transmembrane domain.The COOH-terminal intracellular region contains a proline-rich region. LRP9 mRNA was expressed inthe liver, kidney, lung, and heart at high levels, and in the spleen and brain at low levels. In situ hybridizationanalysis of mouse liver, kidney, and brain detected LRP9 transcripts in hepatocytes, sinusoidal liningcells, peritubular capillaries, choroid plexus, ependyma of the third ventricle, pia matter, and hippocampus.In particular, high levels of expression were observed in the vascular walls. Apolipoprotein E (apoE)-enriched
-VLDL stimulated cellular cholesteryl ester formation in ldl-A7/LRP9. These results raise thepossibility that this newly identified receptor, which is expressed in the liver, may play a physiologicalrole in the uptake of apoE-containing lipoproteins.