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The sorting of acid hydrolases to lysosomes rely on mannose 6-phosphate receptors that cycle between the trans-Golgi network (TGN) and endosomes. The maintenance of this cycle requires the function of the mammalian Golgi-associated retrograde protein (GARP) complex which is composed of three subunits: VPS52, VPS53, and VPS54. Depletion of any of these three proteins, such as by RNAi, impairs the retrograde transport of multiple TGN proteins. VPS53 was identified as an HIV dependency factor (HDF) and plays a role in viral entry to the cell, suggesting that VPS53 may be an important drug target in HIV treatment. At least five isoforms of VPS53 are known to exist.