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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.

A princess prophesied to destroy the world at the age of 16 was abandoned and thrown into chasm right after birth. This, though the truth, was forbidden to be spoken of by anyone in the country.

Edward Elric makes a fatal mistake that drags his brother and his own body into an abyss, and they must seek the philosopher's stone to return their bodies to normal. They learn more and more about alchemy along the way during their adventures.