If you're using IMAP, deletion is a thing. I often get people sending me huge stuff I have no intention to keep or sync. I need to be able to sync the deletion flag. This is a one line change I did myself and used for a long time, but it doesn't get merged because as messages are currently indexed by message-id, tagging a message for deletion might involve more than one actual underlying message.

I also use folders as a mean to exclude useless stuff from syncing. Spam is the most glamorous example: I do not sync spam. I was able to get spam to be moved in/out according to a tag, but only with afew, and again with other issues involved. Doable, but again, ...

Also, notmuch in emacs is very much thread oriented. But with email, I found the behavior very annoying. People will mail you in response to a 1yr old message, and notmuch will happily bring and show the thread from something which is completely unrelated. I found myself switching in/out of tree mode too often, and then just gave up.

I actually enjoyed (and still enjoy) Gnus much more. It's just more efficient for large message volumes. It shows you what's _new_ by default, which notmuch doesn't seem to get right.