Although somewhat speculative, it is tempting to suggest that the interaction between the retromer CSC and TBC1D5 could therefore be an attractive target for therapeutic intervention in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The apparent lack of marked trafficking defects when TBC1D5 is silenced, along with increased recruitment of retromer-associated proteins and reduced APP processing could provide an alternative avenue to explore for those seeking to modulate retromer function in disease states. Further work will be required, however, to develop an effective compound, although the recent structural studies of the TBC1D5-retromer CSC complex (Jia et al., 2016) could enable the identification of a small-molecule inhibitor that could target and disrupt the interaction, thereby mimicking the loss of TBC1D5 function that can be achieved using RNAi.
