We have identified a novel protein, Leprecan-like 1 (LEPREL1), with profound similarity to the Leprecan family of proteo-glycans. The genomic organization of the Leprecan gene family was found to be highly conserved. Expression analysis shows that LEPREL1 is expressed in most tissues as a 3.4 kb transcript encoding an 80 kDa protein. A LEPREL1 specific antibody stains many cell types including adipocytes and neuroendocrine cells of the gastrointestinal epithelium. Muscle tissue contains a specific 6.5 kb transcript and a 200 kDa protein. The 3.4 kb LEPREL1 transcript encodes a 708 amino acid protein containing a signal sequence, four tetratricopeptide repeats (TPRs), a leucine zipper, a P-loop, a prolyl 4-hydroxylase alpha domain (P4Halpha), and a C-terminal KDEL ER-retention motif. LEPREL1 is localized to the ER and Golgi network and over-expressing it affects normal protein disulfide isomerase staining patterns in the ER. (C) 2004 Elsevier Inc. All rights reserved.