While some are not happy with how focused on mythology Assassin’s Creed has become, the Isu have always been a core part of the franchise. They’ve played an important part in every game, even before fans knew too much about the Assassin’s Creed franchise’s First Civilization. Then, of course, everyone knows that Desmond dies at the end of Assassin’s Creed 3, unleashing Juno onto the world (who is stopped later, in the comics by Desmond’s son Elijah).