We report herein the identification of a novel member of the low-density lipoprotein receptor (LDLR) family termed LDLR-related protein 4 (LRP4). Murine LRP4 cDNA encodes a 1113-amino-acid type II membrane-like protein with eight ligand-binding repeats in two clusters. Southern blot analysis of genomic DNA from several different organisms suggests the presence of LRP4 homologues in chicken lacking the gene encoding apolipoprotein E, which is recognized by the ligand-binding repeats of LDLR. LRP4 transcripts were detected almost exclusively in heart in mouse and humans. Despite the presence of the ligand-binding repeats, COS cells transfected with LRP4 did not show surface-binding of beta-migrating very-low-density lipoprotein, suggesting that LRP4 plays a role in a pathway other than lipoprotein metabolism.