Desmond gets away from Abstergo and returns to the Animus to find out what the danger is to his world. He assumes Ezio’s role once more and finds out that Cesare Borgia, the son of the Pope, is after Ezio. Mario is killed during an attack, and the apple is stolen.
Instead of going by himself to respond to this evil, Ezio starts training other Assassins to aid him. When he’s ready, Ezio goes to confront Cesare and watches his foe poison the Pope with the apple. Ezio captures Cesare and retrieves the apple, but Cesare soon escapes and takes the apple with him.
Ezio and his brotherhood of Assassins must go to war against Cesare and his army. Ezio and his forces succeed, and Cesare is thrown to his death. The apple is retrieved, and Ezio finds a safe hiding place for it. He shows this to Desmond through the Animus.
Desmond seeks the apple in the present day, and finds it! He also meets another strange figure. This one is named Juno. She forces him to stab Lucy after learning that she has joined the Templars, and Desmond falls into a coma.