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We never know for sure, it's up to player speculation (as is most of the GTA III era's storyline now that it's over).

After the events of GTA III, you can assume that either the Leone family was disbanded, or Tony Cipriani or Joey Leone took over. Some people say Toni and Joey battled for Don, but the victorious one is under debate. Given that at the start of the game the Leone family was reduced to the size of Forelli Family, it's relatively safe to assume they've been disbanded, facing the growing Triad, Yakuza, Columbians and Diablos.

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