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Pontificating over the header issues may be a moot point but one absolute remains; the OP mentioned that it dumps the cart to RAM and runs it as a ROM image as any other emulator does. Granted anything and everything may change by the time it's released, but that's a fairly gigantic puzzle piece to remove and redesign hardware/software over, and I personally don't see anyone going that far back to the drawing board.
Taking that into consideration means that anything that won't work in a regular copier (or Retrode) won't work in this.
You can't jam a Super Game Boy into a Double Pro Fighter and get a workable ROM image, nor can you use an Action Replay, Game Genie, Magicard, or any other cart based peripheral. No compatibility with copiers or flash cartridges, with the exception of possibly Tototek's flash cart (since you can have it load as a single game with no GUI). Anything with complexity beyond a pin converter won't work.
You won't be able to play any MD stuff from Watermelon (Pier Solar, Project Y, etc) SFT (Beggar Prince, Star Odyssey, etc) and a few other unlicensed companies, you won't be able to play any unlicensed SNES games or some of the oddball, GB, GBC, & GBA titles from Sachen, Gowin, and other companies due to
) The emulators do not support the copy routines
) Even if they did support the routines, the carts cannot be dumped with conventional run of the mill copier tech, so the console can't pull a working ROM image from the cart
Granted that those issues probably do not matter to 99.9% of people in the world, much less the RetroN5's target audience; I'm just disappointed that there's an extremely good possibility that all these clones we've dragged through the mud over shitty sound or colors being off will manage to have more compatibility than something brand new.