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The story is set some time before the events of Uncharted:Drake's Fortune. Nathan Drake is once again the protagonist of the story. Uncover the dark secret behind the 400-year-old massacre of a Spanish expedition as Nathan Drake follows the murderous trail of an ancient and secret Spanish section. Caught in the middle of a rivalry between Jason Dante - his old friend - and Marisa Chase - the granddaughter of an archeologist who has mysteriously vanished without a trace - Nathan races into the treacherous river basins, undiscovered temple ruins and karst caverns of Central America in search of a legendary lost city, only to find himself pushed to the edge of the Golden Abyss.
The game will feature touchscreen controls and motion controls. It was shown to make use the unique Vita features such as use of the front touch panel for climbing and a feature called "Painting" where the player can draw a path for Drake to to climb with their fingers which he'll follow without any further input.