In Bonhoure et al. authors provide strong evidence that a pool of 20s proteasome is released in microvesicles, building upon their previous finding that the 20S proteasome is not released in exosomes. Moreover, they demonstrate that the released 20s proteasome is functional, and can act on proteins with disordered regions such as galectin-3. Authors demonstrate conclusions with very clear data. Furthermore, the text is well written so that someone outside the field can clearly understand the story. Findings are novel and of clear interest to a broad audience of readership. Therefore, this manuscript should be of great interest to the readers of traffic. A few comments remain:

1) Do calpain inhibitors reduce 20s proteosome release in MVs? Showing this would further strengthen the conclusions of figure 3.
2) Is there a significant difference in figure 5B between B2 and B2 + epoxomicin? The text suggests yes but by eye it doesn’t look to be the case. If it is significant, adding statistics (stars/ p values) to the figure will aid in convincing the reader. If not the text stating that the hydrolyzing function of 2 was at least 85% reduced should be accordingly amended.
3) The authors could provide more context/background information on galectin-3, to aid the readers comprehension in their choice.
4) In figure 6B authors claim GAL-2 is not degraded, however there appears to be less at 30 min/1hr. given that the initial band is weaker than gal-3 it is hard to say by eye that it is “not substantially affected” like GAPDH. Densitometric analysis may strengthen authors claim.

Formatting comments:
1) In figure 2 the text refers to left panels and right panels. It would make reading comprehension more fluid to have the p20 fraction as Figure A and the p100 fraction as figure b.
2) The message of figures 1-2 appears to be similar: establishing the context of the story/cementing previous work. Therefore, they could be easily combined into one figure to improve manuscript flow.
3) Is it possible to reorganize figure 3 so it fits in one grouping? It is confusing for the reader to see the same figure number but not the corresponding panel. Same for figure 9.
4) On page 19 “potentially new identified” should read “potential newly identified.”
5) Page 20 :“a similar degradation pattern was obtained using 20S CP purified from red blood cells.” It was not initially clear that authors were referring to figure 6A here, as figure 6 is not called back until the next sentence. Please add figure 6A to the sentence to improve reading comprehension.
6) Page 20 “as an example of potential functional role” should read “as an example of a potential functional role”

Authors have answered all of this reviewers initial comments in a suitable manner and strengthened the manuscript.