Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases

The retromer complex is a highly conserved membrane trafficking assembly composed of three proteins - Vps26, Vps29 and Vps35 - that were identified over a decade ago in Saccharomyces cerevisiae (S. cerevisiae). Initially, mammalian retromer was shown to sort transmembrane proteins from the endosome to the trans-Golgi network (TGN), though recent work has identified a critical role for retromer in multiple trafficking pathways, including recycling to the plasma membrane and regulation of cell polarity. In recent years, genetic, cellular, pharmacological and animal model studies have identified retromer and its interacting proteins as being linked to familial forms of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Here, this commentary will summarize recently identified point mutations in retromer linked to PD, and explore the molecular functions of retromer that may be relevant to disease progression.