He is later contacted by a woman named Daina Le Guin, who guides him to her location. However, before he can remove the straitjacket, Franco is killed and transformed into a Necromorph, leaving Isaac to escape on his own. Isaac Clarke has no memory of the last three years, having just been released by Franco, the protagonist of Dead Space: Ignition.

The game begins in a hospital on the Sprawl, a densely populated metropolis built on a shard of the moon Titan, Saturn's largest moon. Daina Le Guin - A mysterious woman who assists Isaac early in the game and claims to have the means to cure his lethal dementia.Nolan Stross - Another one of the patients held captive by Earthgov, who teams up with Isaac and Ellie to destroy the marker.Hans Tiedemann - Leader of the Earthgov forces on Titan Station, he is the main human antagonist.

Nicole Brennan - Isaac's dead girlfriend, appearing as a hallucination to him at multiple points in the story.

Ellie Langford - A CEC pilot who helps Isaac throughout the game.

Isaac Clarke - The protagonist of the story, survivor of the Ishimura incident and erstwhile captive of EarthGov.

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