VPS29

VPS29, also known as Vacuolar Protein Sorting 29, is a protein encoded by the VPS29 gene in humans and other eukaryotes. It is a core component of the retromer complex, a conserved multi-subunit assembly that mediates sorting and trafficking of transmembrane cargo from endosomes to the trans-Golgi network or to the plasma membrane. In the canonical trimeric complex, VPS29 forms a catalytic subunit that associates with the cargo-selective VPS26-VPS35 subcomplex, helping to recruit and organize cargo and accessory proteins at endosomal membranes.

VPS29 belongs to the metallo-dependent phosphatase family and is thought to contribute metal-dependent phosphatase activity at the endosomal surface. Its exact substrates in vivo are not fully defined, but the catalytic site coordinates divalent metal ions such as zinc or manganese that are required for activity.

VPS29 localizes to endosomes and is stably integrated into the retromer core. Together with VPS26 and VPS35, it helps select cargo and mediate membrane remodeling with sorting nexin proteins to generate tubulo-vesicular carriers for trafficking back to the Golgi or the cell surface.

The retromer complex plays a central role in recycling receptors and lysosomal hydrolases, contributing to proper trafficking and cellular homeostasis. VPS29 and the retromer are conserved from yeast to humans and are essential for multiple endosomal sorting pathways.

Alterations in retromer function, including components such as VPS29, have been implicated in neurodegenerative disease pathways, particularly in studies of Alzheimer’s disease and related disorders, though causal links remain under investigation.

Related topics include the retromer complex and its subunits VPS26 and VPS35.