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>The Media Cache Database is a shared component with Premiere Pro and After Effects, and possibly Encore
Shouldn't that one be left alone, then?
No, because the cache can fill up with outdated, changed and unneeded files. In a worst case scenario, the various projects that reference these files can get confused, and cause unexpected program behavior.
AFAIK, if any of the above programs needs something from the cache that isn't there or isn't right, it will rebuild/modify as necessary.
Cleaning out the cache database also removes pointers to obsolete material.
This can be bad enough with MP3 files, but I discovered it with AIFFs, and I had accumulated 16 gigs of them before I realized what was going on. On an 80 gig drive, that can be a problem. I make a point of going to preferences and dumping these before I shut down the application now.