Aside from the really big one of interstate commerce, there's the smaller issue of participation. Not all otherwise law abiding citizens will participate, either through ignorance or otherwise.
A good example is California, since 1991(maybe 92?) they have required all transfers(very few exceptions) to go through FFLs, but there are still guns in the hands of criminals there. So either all the guns get stolen, or no matter what the rules some people don't know them or don't care about them even if they are otherwise law abiding.
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