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It's the year of destiny and 15 year old Kamui Shiro, a powerful psychic, has returned to Toyko after a 6 year absence. He returns to protect his childhood friends, Fuuma, and Fuuma's younger sister Kotori. But destiny and fate are haunting Kamui and pulling in himself and his loved ones. It is his destiny to decide the fate of the world and mankind, no matter if he wants the role or not.

Sentan Island is a small island surrounded by the Yuden Sea. It exists in a state of dreamlike tranquility, cut off from the war between the Northern Government and the Southern Continent Free Zone. Akiyuki Takehara lives on Sentan Island along with his mother Fusa, He is currently separated from his father, the town doctor Ryuzo, but the bond between father and son remains. One day, after taking Ryuzo the lunch that Fusa has made for him as usual, Akiyuki is caught up in an explosion along with his friends, Haru and Furuichi. The explosion produces a mysterious light which enters Akiyuki's arm, causing him excruciating pain. He's given no time to understand it, however, as the white-haired girl who rode on the bus with him guides him to a power unlike anything he's ever known. He transforms into a creature called Xam'd, and his rampage is only stopped when a red-haired foreign girl appears and warns him that he'll turn to stone if he doesn't go with her.

4000 years have passed since humanity abandoned Earth. Forced to fight an alien life-form, Gnosis, mankind developed KOS-MOS - a battle android with amazing capabilities. When a ship carrying the android is being attacked, KOS-MOS gets activated and saves it's creator, Shion Uzuki. But KOS-MOS doesn't want to follow her orders and executes some unknown plan. After their ship is destroyed, Shion and her companions find themselves thrust into the middle of a battle with Gnosis, U-TIC Organization and their own superiors, a battle with no clear sides...

Kimihiro Watanuki is a young boy with a cursed gift. He has the ability to see evil spirits, and somehow they seem attracted to himself. One day he meets a mysterious woman who names herself Yuuko. She claims to have the means to end his torment, but she never works for free, and she wouldn't help him until he works for her enough to pay for her services. Thus he starts to work in her shop and discovers that in that place, nothing is what it seems.