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.
Keywords: Cathepsin D, endosome, Parkinson's disease, retromer, sorting nexin, Vps35 p.D620N, Vps35 p.R524W.
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