Thumb driver enumeration might be different on each machine -- how does Thunderbird find its profile?

Handling of drive letter changes is one of the primary requirements for apps officially released here.

The way this works is that our Launcher stores where it was last run from, then compares it to where it is currently running from, and updates the fields within the app's data if it needs to before launching the actual app.

For most (if not all) official apps this will also work changing the entire path (eg C:\PortableApps\ to D:\Apps\Portable\), not just the drive letter.