IGF2R, also known as the cation-independent mannose-6-phosphate receptor, is found ubiquitously in human tissues with a truncated soluble form of the receptor present in the circulation. Full-length, 300-kDa, IGF2R comprises a large N-terminal extracellular region of 15 homologous domains, a single membrane-spanning region and a small cytoplasmic tail. In addition to IGF-II binding, major IGF2R functions include sorting newly synthesized lysosomal enzymes and endocytosis of extracellular lysosomal enzymes. To perform these disparate functions, the extracellular region contains binding sites for IGF-II and phosphomannosyl residues