Desmond Miles is dead at the sake of delaying a further catastrophe from happening. Juno, a slave master from the First Civilization seeks to destroy this world and purge the world into eternal slavery. Minerva, seeing through her apparent lies of salvation had provided the Assassins a new light. A way to resurrect Desmond Miles.
Now, with Desmond dead, who will commandeer the Animus? There was only one person: his father, William Miles. With instruction given from Minerva, they sought out to find an artifact created by the humans to fight off the First Civilization and granted the mortal humans the ability of resurrection. Its whereabouts are unknown, but it was traced to an Assassin in the present day third-world country; the Philippines.
Difficult part is, he hid it during the 18th Century. And he is most probably dead. Well, that's what the Animus is for.
With the remaining Assassins, William and his band of Assassins uncover this new artifact to resurrect Desmond, their most prized savior. As well as uncovering the Miles' Philippine bloodline.