Win+E has worked correctly for ages but yesterday it stopped working as expected and opens File Explorer instead
The only "major" change I have made was creating a new toolbar (a copy of my customised Menu toolbar) which I have now deleted. I doubt that has anything to do with it as Win+E is not associated with that toolbar.
Win+Shift+E and Ctrl+E work as expected.
I have deleted the Win+E hotkey and recreated it but it still does the same.
If you're on Windows 10, using Preferences / Launching Opus / From the Win + E hotkey is usually more reliable than trying to override the system hotkey directly.
Yes, it needs Explorer Replacement to function so it would only work with USB if that was turned on via the special USB ini file (with the usual caveats about turning that on for USB).
We make changes to keep the Win + xyz hotkeys working with different Windows versions (including different Win 10 updates), so updating is a good idea before trying anything else.
(Or just avoid the Win + xyz hotkeys entirely, TBH, for an easier life. We aim to keep them working, but it seems there will always be times when a new Windows update breaks them, unless Microsoft ever decide to add a proper way for users to customize what they consider to be system hotkeys.)