There are a myriad of possible causes. And "not responding" issues have plagued Thunderbird for a long time. Generally these issues come for folk not compacting their storage, or the compact failing to complete. Or contention issues getting access to the storage files to actually perform the function. This is also a leading cause of compact failures. The leading cause of these contention issues is the ubiquitous antivirus product that is scanning this huge file every time it changes. They are inherently slow, taking something like 10 minutes per gigabyte. Lots of folk have an inbox that is more than a few Gigbytes in size and updated every 10 minutes or so. Then updates again to remove junk, move mails or delete them using filters (two more updates) all before you the user actually get a look at the mail to interact with it. The upshot is we recommend you exclude the Thunderbird mail and IMAPmail folders, but preferably the entire Thunderbird profile folder, from this on access scanning to prevent this contention. There are detailed diagnostic steps here https://wiki.mozilla.org/Thunderbird:Testing:Memory_Usage_Problems They are show in relation to memory there, but really they are fairly generic.