Insulin-like growth factor 2 receptor (IGF2R) (IGF2R)

The Insulin-like growth factor 2 receptor (IGF2R), also known as the cation-independent mannose-6-phosphate receptor (CI-MPR), is a multifunctional transmembrane glycoprotein (UniProt P11717). It is primarily responsible for the trafficking of mannose-6-phosphate (M6P)-tagged lysosomal enzymes from the trans-Golgi network to lysosomes and the internalization of extracellular M6P-containing proteins via endocytosis. Additionally, it acts as a clearance receptor for insulin-like growth factor 2 (IGF2), internalizing and directing it for degradation to prevent excessive signaling through the IGF1 receptor (PubMed: 25100792). This dual functionality makes it a critical target for enzyme replacement therapies (ERTs), such as Alglucosidase alfa, which are engineered with M6P residues to ensure delivery to the lysosome (NCBI Gene: 3482). In many cancers, IGF2R functions as a tumor suppressor, and its downregulation or mutation is associated with increased cell proliferation and tumor progression (PubMed: 11432825).

Other names

Cation-independent mannose-6-phosphate receptorCI-MPRM6P/IGF2 receptorCD222MPRIMannose-6-phosphate receptor (cation independent)

The receptor mediates the internalization of mannose-6-phosphate-tagged proteins and the sequestration of IGF2, directing them to the lysosomal compartment for processing or degradation (PubMed: 18425444, 25100792).