Vacuolar protein sorting 39 homolog (VPS39)

Vacuolar protein sorting 39 homolog (VPS39), commonly abbreviated as VPS39, is a conserved protein subunit of the hexameric HOPS (Homotypic Fusion and Protein Sorting) tethering complex[1][2][3][4]. The HOPS complex mediates the tethering and fusion of lysosome-like vacuole membranes with incoming vesicles, a key step in endolysosomal trafficking and lysosomal biogenesis[1][3][4]. VPS39 has a modular architecture, including N-terminal β-propeller and C-terminal α-solenoid domains, and binds directly to membrane-anchored small GTPases such as Rab7 (Ypt7 in yeast)[3][4]. It also plays a role in the formation of membrane contact sites (MCSs) between vacuoles and mitochondria (vCLAMPs), independent of other HOPS complex functions[1]. The availability of VPS39 is dynamically regulated between its roles in HOPS-mediated membrane fusion and vCLAMP formation[1]. There is no current evidence that VPS39 is a direct therapeutic target or that it interacts with drugs, but as a central node of lysosomal trafficking and organelle communication, alterations to VPS39 or HOPS complex function could impact neuronal health, autophagy, and potentially contribute to certain disease mechanisms[3][4].

Other names

Vam6/Vps39-like proteinKIAA0770TLPVAM6hVam6pTRAP1-like proteinHOPS complex subunitvam6/Vps39-like protein