studies of i-cell disease led to the discovery of the receptors that bind to this specific tag. firstly the ci-mpr was discovered and isolated through the use of affinity chromatography. however scientists discovered that some of the lysosomal enzymes still reached the lysosome in the absence of the ci-mpr. this led to the identification of another mannose 6-phosphate binding receptor, the cd-mpr, which binds its ligand in the presence of a divalent cation such as mn.