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Gurren Lagann takes place in a fictional future where Earth is ruled by the Spiral King, Lordgenome, who forces mankind to live in isolated subterranean villages. These villages have no contact with the surface world or other villages, and are under constant threat of earthquakes.

The story takes place in Seikyou Private School. A facility that consists of multiple buildings that connect together to accommodate both junior and senior high school students.

The school romantic comedy revolves around a second-year high school student named Sorata Kanda who lives in Sakurasou, the dormitory for problem children at Sorata's school. One day, Mashiro Shiina—a cute girl who happens to be also a cosmopolitan, brilliant artist—moves into Sakurasou.

Subaru finds himself in a fantasy world. He thinks he's supposed to be a big hero as the protagonist from many types of anime.

Due to an untimely death of one of its members, a once happy and playful group of friends drifted and grew apart. Living their lives separately from each other, they secretly blame themselves for the horrible accident, and never got to move on even after years had passed.

After death, humans are either sent to the void or reincarnated. But for some, at the instant of their death, they arrive at Quindecim, a bar attended by the mysterious white-haired Decim.

Tomoya is labelled as a delinquent at his school because he is constantly late and skips classes, but he seems to have little care about how others perceive of him. Everything in his life seemed dull and unchanging until one morning he meets Nagisa Furukawa on the road to his school; he finds her muttering to herself to give her more motivation for the school day.