Never seen such a thing on this forum. Although the location of the file might be an issue. I have seen odd things with files stored on remote locations or in synchronized folders. Files are sometimes just not available and Thunderbird software does not appear to report that anywhere but the error console with all the other rubbish. (not available because of network contention or simply just does or the anti virus is holing it up for a scan)

Many thanks, Matt. Your reply got me thinking. We use Dropbox for all our work files, and it occurred to me that she might have her signature somewhere in Dropbox. I've asked her to make sure her signature file is stored locally on her Mac, which she's doing, so hopefully this will solve the problem.

No guarantees, but there are issues with networked storage. There is bug I was reading about settings not being saved and another support topic about temp files for prefs.js, so there is some sort of issue or issues. But I have seen nothing concrete as to what or why.