I wish thunderbird supports native reply reminders like in gmail/outlook. I always have to remind myself to follow up with people who haven't replied to my emails. I've been using threaded messages to combat this, but it gets kind of messy when email chains get lengthy.
Also, I wish there were more tutorials online for workflow processes on thunderbird. With more funding by mozilla and dev support, I hope people make higher quality tutorials online, many of them are highly dated.
More robust addons. I've tried dozens but I currently only use 2 now, one for attaching images with website URLs and another for image-previewing multiple attachments.
I haven't really bothered compressing anything because it freezes my PC everytime. I set everything to IMAP, my localstorage on thunderbird is about 100 GB since I send out and receive a lot of large files. It's not a great way of handling things, but it works since my server has a 3 million file limitation. Storage is cheap, but security is nonexistent in this regard.
Automation with autothreading would definitely be a nice feature. I personally don't use any autotagging in any email system, I normally just rewrite subject headers instead / use filters alot / get better at searching.
Fuzzy searching really needs some work. Usually, I will know exactly what email to search for (be it an automated subject header with a unique identifier, or a person I deal with), but I cannot find it on my first try.
Second, from a UX design prospective, I wish thunderbird would have an accordion-like collapsible method for threaded messages, indicated by a "..." in the UX. For instance, I might have a 10+ chain response email, I only need to see the first 2 emails sent, and the last 2 in the chain, not the 6 in the middle (collapse by default). This is mostly for items that need a lot of clarifications.
UX needs improvement for handling multiple emails. As of now , I just forward every email to my main email and filter out appropiately. I don't see a better way of doing things in thunderbird.
Thunderbird doesn't support threaded messages outside main inbox, AFAIK.
Baynesian junk filter could use some improvements as well. Some vendors will mix spam and important mail from the same email address. Thunderbird doesn't do a great job filtering these out, even after training junk filter consistently.