The second chapter of Assassin’s Creed brings Desmond to the 15th century Italy during the Renaissance period. With the help of Dr. Vidic’s assistant, Lucy (revealed to be an undercover agent for Present-Day Assassins), Desmond escapes the clutches of Dr. Vidic.

Lucy’s updated version of Animus as well as her secret team put Desmond, once again, on a mission. He is now living the memories of his ancestor, Ezio Auditore da Firenze, a man seeking revenge on the part of his executed family members.

Enzio learns that he is part of a family line of Assassins. He trains to become an Assassin himself and journeys across Italy seeking vengeance. During his journey, Ezio encounters allies in Niccolo Machiavelli and Leonardo da Vinci. As Ezio confronts his final adversary, the Grandmaster of the Templar's; Rodrigo Borgia.

He learns of Borgia’s plot to open what he calls the “Vault” which contains great and influential power. He also discovers two Pieces of Eden in Borgia’s possession – an Apple of Eden and Borgia’s papal staff.

Borgia escapes from Ezio with the staff but Ezio remains in possession of the Apple. Desmond now jumps to a later memory of Ezio’s, where Borgia is now Pope Alexander VI. Ezio breaches Vatican City and beats Borgia in hand-to-hand combat, gaining the papal staff and letting Borgia live.

Using the two Pieces of Eden, Enzio opens the “Vault” and is introduced to Minerva, a member of the “First Civilization.”

He learns that the purpose of the Pieces of Eden and is told that he will be responsible for fulfilling the “prophecy.” A gripping and dramatic ending point peaks when Dr. Vidic and Abstergo locate Desmond and the team in Present Day, causing this chapter to end with the protagonists on the run and mention of an approaching cataclysmic event threatening Present Day earth.

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