FWIW.. I run in off external drive. No issues at all. Just make sure you keep the expected folder naming structure.
I don't want to sound like an IKM sales rep. But where it's handy for me is it allows me to work on ideas from just one interface. I do more traditional folk, rock music. So having access to al those sampled instruments with some rudimentary t-racks effects interface is handy for me. I don't do much sound design or experimental stuff. Just a lot of arranging and rudimentary orchestration. I recently get into using it for its multi functionality and that sort of opened up some new possibilities. When I start working on a new track, its usually one of the first things I load up.