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

The Cation-independent mannose-6-phosphate receptor (CI-MPR), also known as the Insulin-like growth factor 2 receptor (IGF2R), is a large transmembrane glycoprotein that plays a pivotal role in the trafficking of lysosomal enzymes [1, 2]. Its primary function is to recognize and bind mannose-6-phosphate (M6P) residues on newly synthesized acid hydrolases in the trans-Golgi network, facilitating their transport to the endosomal-lysosomal system [2, 4]. Additionally, CI-MPR is expressed on the cell surface, where it captures extracellular M6P-tagged proteins and internalizes them via receptor-mediated endocytosis [4]. This pathway is the fundamental mechanism for enzyme replacement therapies (ERTs), such as Elosulfase alfa (recombinant GALNS), which are engineered with M6P glycans to ensure delivery to the lysosomes of affected cells in patients with Morquio A syndrome [3, 5]. Beyond its role in enzyme transport, the receptor also acts as a clearance factor for insulin-like growth factor 2 (IGF2), thereby regulating cell growth and acting as a putative tumor suppressor [1, 2]. In the context of recombinant GALNS uptake, the receptor serves as the essential conduit for therapeutic efficacy by bridging the extracellular drug to its intracellular site of action [3]. Therapeutic challenges associated with this target include the potential for immunogenicity against the delivered enzymes and the requirement for high-affinity M6P-binding to achieve clinical efficacy [3, 5].

Other names

Insulin-like growth factor 2 receptorIGF2RM6P/IGF2 receptorCD222Mannose-6-phosphate receptor (cation independent)

Receptor-mediated endocytosis and lysosomal delivery