VPS35

thumb|Figure showing the retromer complex. The retromer complex recognizes cargo from the endosome. The VPS35-VPS26-VPS29 trimer forms the cargo recognition complex of the retromer. Vacuolar protein sorting ortholog 35 (VPS35) is a protein involved in autophagy and is implicated in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). VPS35 is part of a complex called the retromer, which is responsible for transporting select cargo proteins between vesicular structures (e.g., endosomes, lysosomes, vacuoles) and the Golgi apparatus. Mutations in the VPS35 gene (VPS35) cause aberrant autophagy, where cargo proteins fail to be transported and dysfunctional or unnecessary proteins fail to be degraded. There are numerous pathways affected by altered VPS35 levels and activity, which have clinical significance in neurodegeneration. There is therapeutic relevance for VPS35, as interventions aimed at correcting VPS35 function are in speculation.

== Gene == In humans, VPS35 is transcribed on chromosome 16q11.2 where is spans about 29.6 kilobases and contains 17 exons. It is evolutionarily conserved and required for survival, as mouse knockout studies have demonstrated embryonic lethality. VPS35 levels peak at postnatal days 10-15 and then decline to a low, stable level throughout adulthood. RNA expression of VPS35 is ubiquitous throughout the body, but are higher in the brain, heart, gonads, spleen, and skeletal muscle, and lower in the lung, liver, kidney, and blood leukocytes.left|thumb|298x298px|Crystal structure of the cargo recognition complex. VPS26 (yellow), VPS35 (light blue), and VPS29 (light purple) form a trimer. VPS35 is bound by VPS26 at its N-terminus and by VPS29 at its C-terminus.