Cation-independent mannose-6-phosphate receptor (CI-M6PR) (CI-M6PR)

The cation-independent mannose-6-phosphate receptor (CI-M6PR), also known as the insulin-like growth factor 2 receptor (IGF2R), is a multifunctional transmembrane glycoprotein essential for the trafficking of lysosomal enzymes (UniProt P11717). It primarily functions at the trans-Golgi network to divert newly synthesized acid hydrolases to lysosomes and at the plasma membrane to internalize extracellular M6P-containing ligands via endocytosis (Ghosh et al., 2003, Nature Reviews Molecular Cell Biology). This cellular uptake interface is the pharmacological basis for enzyme replacement therapies (ERTs), where recombinant enzymes are glycoengineered with M6P residues to ensure delivery to the lysosomal compartment of target cells (Coutinho et al., 2012, Molecular Genetics and Metabolism). Beyond enzyme transport, the receptor acts as a clearance factor for IGF2, thereby modulating growth signaling and acting as a putative tumor suppressor (NIH/NCI). In clinical practice, CI-M6PR is targeted to treat various lysosomal storage diseases, including Pompe disease and Mucopolysaccharidosis, by facilitating the entry of therapeutic enzymes into deficient tissues (PubMed 11085999). The receptor's ability to bind multiple ligands, including TGF-beta and plasminogen, also implicates it in tissue remodeling and fibrotic processes (StatPearls).

Other names

Insulin-like growth factor 2 receptorIGF2RM6P/IGF2 receptorCD222MPR 300Mannose-6-phosphate receptor (cation independent)

Facilitates the internalization of mannose-6-phosphate-tagged recombinant enzymes from the extracellular space into the endolysosomal system via receptor-mediated endocytosis.