Why do Mail preferences get lost on reboot? Apple Mail, the OS bluetooth subsystem and some other applications (e.g. Fantastical) loose relevant (but not all) configuration and preferences on nearly every reboot. For Apple Mail it seems that all lost settings are stored in the file ~/Library/Containers/com.apple.mail/Data/Library/Preferences/com.apple.mail.plist. I haven't yet identified the other affected files.
What could cause the file contents to be lost on nearly every reboot? It does not happen if I hunt for it (keep rebooting), but only after using the Mac for a while.
I currently run macOS 10.15.6 on a MacBook Pro 16&quot; with only a few popular Apps from the App Store plus Microsoft Office.
I am a long term Mac user. The bad behavior started approximately 2 years ago after an update to macOS High Sierra (I think). The Mac became more an more unusable because of this and other strange bugs (it also started to become extremely slow, so I had to reboot regularly, loosing all settings afterwards). Repairing and even installing the OS did not help. Therefore, I got a new Mac and installed everything from scratch (no restore from a backup) and installed only very little software on the system. However, the preferences still get lost on nearly every reboot!
This is user level corruption or system level corruption in almost all cases. Sometimes it’s third party software, but that’s the hardest to trace, so focus on the easy steps first.

get a backup
Make a new user account and see if that user can maintain mail settings across reboots.

Based on that you’ll know if you need to address your user preferences, repair the disk, erase the disk and reinstall the os. After reinstalling, don’t set up the mac or restore the backup - just test the system with mail.
Then decide to wipe a second time and restore files / users or if you are better off setting up a clean system just transferring documents from the backup.