Cation-dependent mannose-6-phosphate receptor

The cation-dependent mannose-6-phosphate receptor (M6PR) is a 30.9 kDa soluble receptor that mediates the trafficking of lysosomal hydrolases. It functions by binding phosphomannosyl-tagged enzymes in the Golgi apparatus and transporting the receptor-ligand complex to acidic prelysosomal compartments, where pH-dependent dissociation releases the cargo for lysosomal delivery (UniProt: P20645).

M6PR is involved in the fundamental cellular process of lysosomal biogenesis and enzyme trafficking. Its role in maintaining lysosomal function implicates it in cellular clearance mechanisms relevant to protein quality control and organellar homeostasis.

M6PR is associated with Alzheimer's disease (Chaparral AD proteomics). Proteomic analysis of post-mortem AD brain tissue demonstrates that M6PR is significantly upregulated compared to age-matched controls, with a mean log2 fold-change of 0.83 across one subcellular fraction in a TMT-labeled DDA proteomics experiment examining four subcellular compartments (P2, P3, S2, S3). This upregulation may reflect compensatory changes in lysosomal processing or alterations in protein trafficking pathways in the AD brain.