We report herein the identification of a novel member of the low-density lipoprotein receptor (LDLR) family termed LDLR-related protein 4 (LRP 4). Murine LRP 4 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 LRP 4 homologues in chicken lacking the gene encoding apolipoprotein E, which is recognized by the ligand-binding repeats of LDLR. LRP 4 transcripts were detected almost exclusively in heart in mouse and humans. Despite the presence of the ligand-binding repeats, COS cells transfected with LRP 4 did not show surface-binding of β-migrating very-low-density lipoprotein, suggesting that LRP 4 plays a role in a pathway other than lipoprotein metabolism.