Cation-dependent mannose-6-phosphate receptor (CD-MPR)

The cation-dependent mannose-6-phosphate receptor (CD-MPR), also known as the 46 kDa mannose 6-phosphate receptor (MPR 46), is a type I transmembrane glycoprotein and a member of the P-type lectin family (UniProt: P20645). Its primary biological role is the recognition and transport of newly synthesized lysosomal acid hydrolases from the trans-Golgi network (TGN) to pre-lysosomal/endosomal compartments (PubMed: 11190678). Functioning as a homodimer, the CD-MPR requires divalent cations such as manganese for optimal binding affinity to its mannose-6-phosphate (M6P) tagged ligands, distinguishing it from the larger cation-independent receptor (PubMed: 12493773). In disease states, the CD-MPR is critical for preventing lysosomal storage disorders (LSDs); the combined deficiency of both M6P receptors leads to the massive extracellular secretion of enzymes and subsequent cellular accumulation of undegraded substrates (NCBI: Gene ID 4074). As a therapeutic target, it is the intended destination for enzyme replacement therapies (ERTs) like alglucosidase alfa and avalglucosidase alfa, which are bioengineered with M6P residues to exploit receptor-mediated intracellular sorting (PubMed: 38086445). Current pharmacological strategies often focus on enhancing the M6P-tagging density of therapeutic proteins to maximize receptor binding and optimize lysosomal delivery.

Other names

46 kDa mannose 6-phosphate receptorMPR 46M6PRSmall mannose 6-phosphate receptorCD-M6PR

The receptor facilitates the targeted delivery of mannose-6-phosphate (M6P)-tagged lysosomal enzymes by binding them in the trans-Golgi network or at the cell surface and transporting the receptor-ligand complex to acidic endosomal compartments, where pH-dependent dissociation allows the enzymes to reach the lysosome.