C:\Users\JLT\AppData\Roaming\Thunderbird\Profiles\2yp8vhmy.default\ImapMail\mail.runbox.com

Presumably that's a folder? Please confirm which file(s) have a large size.

Before anything else, I'd create a full backup of the Thunderbird profile. https://support.mozilla.org/kb/profiles-where-thunderbird-stores-user-data#w_backing-up-a-profile

In general, to avoid mail folders (particularly Inbox) growing too large tell Thunderbird to automatically compact folders. http://kb.mozillazine.org/Compacting_folders

Note, compacting large files may take a while.

395gb is a lot to back up. If it is truely an imap account then we shouldn't need to back up the ImapMail\mail.runbox.com account folder. But yeah, backing up the rest of the profile would be a good idea.

I would forget about compacting - that would take forever, if it even worked at all. What I want to know ,before you blow anything away, is what are the 4-6 largest files in ImapMail\mail.runbox.com ??

I tried one last thing before more radical measures. I went through all 100+ files in the mail.runbox.com folder abd found one that was 360GB. I went back into Thunderbird and deleted that item. That solved the problem.

And...

What was the filename (X) of that large file? Was there a corresponding X.msf file, i..e was it a "real" mail folder?