I don't know if this helps anyone, but it seemed to fix my issue with this exact same thing.
I have a project file for a 3D software (Unreal Engine) on an external SSD, which I have used to be able to work on the project remotely. When I have worked on the same project on my main PC, with the project on my main drive, I can save and modify the project file as expected. When I put the project on the external SSD, and then tried to save the project after working for a while, the software would simply freeze, with no error message being displayed. I would have to force quit the program, and the changes I made wouldn't be saved.
After trying everything I could find online, I decided it might be best to start from square one and format the drive. I had originally formatted it as exFAT, but when I formatted it this time, I changed it to NTFS. I had never noticed this before, but when it was exFAT, I had no Security tab in Properties, and I couldn't seem to change any permissions for the drive. When it was NTFS, I had all those options available.
I went into properties, enabled all permissions for all users, and then copied my project onto the drive again. I just worked in it for a minute, making some definite changes, and I was able to save the project file as normal, while working off that drive. :)
Maybe this helps someone.