Vacuolar protein sorting-associated protein 52 homolog

VPS52 (Vacuolar protein sorting-associated protein 52 homolog) is a component of the GARP and EARP protein complexes involved in intracellular membrane trafficking. It functions in retrograde transport from endosomes to the trans-Golgi network and in endocytic recycling, helping maintain proper sorting of lysosomal hydrolases and recycling of receptors such as transferrin receptor to the plasma membrane (UniProt: Q8N1B4).

The protein operates within the secretory and endosomal pathways, which are critical for cellular homeostasis and protein quality control. These trafficking pathways are essential for proper lysosomal function and protein degradation, processes that become dysregulated in neurodegenerative disease.

VPS52 is downregulated in Alzheimer's Disease brain tissue. In a proteomic analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled mass spectrometry across four subcellular fractions, VPS52 showed reduced abundance with a mean log2 fold-change of −0.37 (Chaparral AD proteomics). This downregulation may reflect impaired endosomal-lysosomal trafficking capacity in AD, potentially contributing to the accumulation of misfolded proteins characteristic of the disease.