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So my question is: Can I run Zorin off of a hard drive other than the C: drive?
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The only way you could run Zorin on your "C drive" is using VirtualBox or other virtual software. If you don't want to do that, you need to put it on its own partition.
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Is the install persistent so that changes are kept?
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If you mean by that installing as suggested to a separate partition on another drive then of course it would.
You can share folders between the systems. You can read/write to windows ntfs partitions from Linux but the reverse doesn't work that I know of unless you get some third party software. windows doesn't recognize Linux filesystems.
You keep referring to VirtualBox so I'm not sure if I'm understanding what you want to do.