Sorting protein-related receptor (SorLA/LR11) is a highly conserved mosaic receptor that is expressed by cells in a number of different tissues including principal cells of the collecting ducts in the kidney and neurons in the central and peripheral nervous systems. SorLA/LR11 has features that indicate it serves as a sorting receptor shuttling between the plasma membrane, endosomes, and the Golgi. We have found that a fraction of SorLA/LR11 that is synthesized in the kidney and the brain bears N-linked oligosaccharides that are modified with terminal ␤1,4-linked GalNAc-4-SO 4 . Oligosaccharides located in the vacuolar sorting (Vps) 10p domain (Vps10p domain) are modified with ␤1,4-linked GalNAc when the Vps10p domain is expressed in cells along with either of two recently cloned protein-specific ␤1,4GalNAc-transferases, GalNAcTIII and GalNAcTIV. Either of two sequences with basic amino acids located within the Vps10p domain is able to mediate recognition by these ␤1,4GalNAc-transferases. The highly specific modification of oligosaccharides in the Vps10p domain of SorLA/LR11 with terminal GalNAc-4-SO 4 suggests that this unusual modification may modulate the interaction of SorLA/LR11 with proteins and influence their trafficking.Sorting protein-related receptor (SorLA), 2 also known as LR11, is a highly conserved mosaic, type 1 receptor. The luminal/extracellular domain consists of a short NH 2 -terminal sequence preceding a consensus site for furin cleavage, a vacuolar sorting (Vps) 10p domain, 5 F/YWTD/␤-propeller modules, an epidermal growth factor precursor sequence, 11 low density lipoprotein receptor (LDLR) class A (LDLR-A) repeats, and 6 fibronectin type III repeats (1, 2). The single transmembrane domain is followed by a 54-amino acid cytosolic domain containing a motif that mediates interaction with GGA (Golgilocalized, ␥-ear containing, ARF binding) proteins involved in Golgi-endosome sorting (3). The presence of these varied domains places SorLA/LR11 in a number of different families and underscores its ability to interact with a range of different ligands. A Vps10p domain is also present in the receptors sortilin-1 (4) and SorCS (5). The Vps10p domain of SorLA/ LR11 mediates the endogenous binding of the propeptide released from the N terminus of SorLA/LR11 by furin cleavage. The peptides neurotensin and hydra head activator also bind to the Vps10p domain (6). The YWTD repeats, epidermal growth factor repeat, and the LDLR class A repeats are characteristic of LDLR family members (7) and likely mediate apolipoprotein E and receptor-associated protein binding by SorLA/LR11 (6). In addition, the 6 fibronectin type III repeats are characteristic of a number of neural adhesion molecules (2).The peptide portion of SorLA/LR11 consists of 2215 amino acids with a calculated molecular weight of 247,000. The receptor migrates with M r of over 300,000 when examined by SDS-PAGE indicating that a large fraction of the 20 potential Asn-glycosylation sites present on the luminal domain are utilized. We have determin...