VPS35n

VPS35n is a protein that belongs to the vacuolar protein sorting 35 (VPS35) family, which plays a central role in the regulation of endosomal protein trafficking in eukaryotic cells. It has been identified in several model organisms, including mammals and plant species, and is typically encoded by a gene that is evolutionarily conserved across diverse taxa. Structurally, VPS35n is approximately 400 amino acids in length and contains several HEAT repeats that facilitate protein–protein interactions. It is a peripheral membrane protein that associates with the cytoplasmic face of endosomal membranes.

In mammals, VPS35n is a core component of the retromer complex, which is responsible for sorting transmembrane cargo from endosomes back to the trans-Golgi network or to the plasma membrane. Co‑immunoprecipitation studies have shown that VPS35n interacts with VPS26 and VPS29, the other established subunits of retromer, stabilizing the complex and enabling efficient cargo recognition. Functional assays in model cell lines demonstrate that depletion of VPS35n reduces the recycling of key receptors such as the transferrin receptor, leading to altered endolysosomal degradation pathways.

Mutational analyses have revealed that missense variants of VPS35n are linked to neurodegenerative phenotypes in humans. A recurrent mutation, Asn^93Ile, associated with a subset of Parkinson’s disease cases, alters the binding affinity of VPS35n for specific cargo proteins, thereby compromising cellular protein homeostasis. Mouse models carrying analogous mutations display behavioral and pathological features that mirror human disease, underscoring the importance of VPS35n in neuronal maintenance.

Research on VPS35n also extends to plant biology, where homologs of this protein are required for efficient trafficking of auxin transporters. Loss‑of‑function mutants exhibit developmental defects, indicating that VPS35n has conserved roles in hormone signaling and growth regulation.

In summary, VPS35n is a versatile component of the endosomal sorting machinery, essential for maintaining cellular protein quality control and implicated in human neurodegenerative disorders.