Mannose 6-phosphate (M6P) is a critical glycosylation marker primarily involved in the Golgi processing of lysosome-targeted proteins. After synthesis in the rough endoplasmic reticulum, the oligosaccharide chains of these proteins undergo phosphorylation to generate the M6P signal. This signal is then recognized and bound by M6P receptors (MPRs) on the Golgi membrane, facilitating vesicular transport to deliver the proteins to lysosomes. This mechanism is essential for the proper sorting of lysosomal enzymes. Dysfunction in this pathway (e.g., defective M6P generation or receptor mutations) can lead to lysosomal storage disorders, such as I-cell disease. The discovery of the M6P pathway has advanced the understanding of intracellular protein sorting and metabolic diseases, and it is also being explored for targeted delivery applications in gene therapy.
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