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Natsume Yuujinchou centers on Takashi Natsume, a young man who can see youkai, spirits invisible to most. He's inherited a powerful artifact from his late grandmother, Reiko: the Book of Friends, a list containing the names of youkai she defeated and bound to her will.
Burdened by this inheritance and his ability, Natsume struggles to connect with others. He makes a bargain with a powerful youkai named Madara, nicknamed Nyanko-sensei, for protection.
Together, Natsume and Nyanko-sensei embark on a journey to return the names in the Book of Friends to their rightful owners, the youkai themselves. Along the way, Natsume begins to form bonds with both humans and youkai, slowly opening himself up to the world around him.