I can't say for sure, but my guess is you won't be able to make skins that consist of extreme pixel color variety next to each other ( black, green, yellow, blue, red, ... for example ).
As as far I have uncovered they use a rectangle blitting technique which allows a BG & FG Color per Rectangle. So extreme color changes per rectangle (checkboard style for example) will work just fine.
But for a normal texture, where you don't need hard color changes every pixel, I guess this format will be as unproblematic as those of other games we are and have been messing with.
This is only an estimate, and there is still much info to be uncovered. But without this info, nothing I say is 100% accurate, please be aware of that.