C11orf2 Inhibitors

The VPS51 protein is a subunit of the Golgi-associated retrograde protein (GARP) complex, which is crucial for the tethering and fusion of endosome-derived transport vesicles with the trans-Golgi network (TGN). The GARP complex, composed of VPS51, VPS52, VPS53, and VPS54, is conserved among eukaryotes and plays an essential role in the retrograde trafficking pathway that recycles proteins from endosomes to the Golgi apparatus.VPS51, specifically, is necessary for the stability and function of the GARP complex. It assists in the recognition and binding of vesicles coming from endosomes, ensuring that cargo proteins are appropriately sorted and delivered back to the Golgi. This retrograde transport is critical for the maintenance of Golgi dynamics, the recycling of sorting receptors, and the retrieval of escaped endoplasmic reticulum (ER) proteins that are to be returned to the ER from the Golgi.

The function of VPS51 and the GARP complex is essential for the overall vesicular trafficking within a cell, which includes the processing and sorting of lysosomal enzymes, the recycling of mannose 6-phosphate receptors, and the maintenance of lysosome identity. Disruptions in the GARP complex, and therefore in VPS51 function, can lead to various cellular dysfunctions and have been associated with certain human diseases, such as the neurological disorder progressive cerebello-cerebral atrophy type 2.At the molecular level, VPS51 interacts with the other GARP subunits to form a stable complex, and this interaction is necessary for the localization of the complex to the TGN. The complex serves as a platform that facilitates the SNARE-mediated fusion of vesicles, by bridging the vesicles to the Golgi membrane, a critical step in vesicular trafficking that maintains cellular homeostasis.