The story of the distant future. The human has lived in the underground for a long time. Simon, the boy who digs to expand the village, finds a shining small drill. Kamina, the guy who lives in the village same as Simon, yearns for the ground.

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With the mysterious Lagann in hand, Kamina and Simon take Yoko back to her home village of Ritona. Life on the surface world catches up to Kamina and Simon, as they find themselves assisting in defending against a new Gunman threat and the Beastmen who pilot them.

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Yoko goes hunting with Kamina and Simon. They encounter a beastman named Viral in a hunting-ground.

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Team Gurren sets out to face Viral.

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Team Gurren's continuing journey brings them to an underground village, where society mandates a humbling existence and the worship of Gunmen as divine beings. After leaving the village, Team Gurren is joined by Rossiu, the adopted son of the village chief, and two children, Gimmy and Darry.

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Having picked up new members in their last adventure, Team Gurren continues onwards to the Gunmen rallying point. However, not everything is as it seems to be at a slight pit stop at a hot springs getaway in the middle of nowhere.

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More details of the Beastman Empire are revealed as Thymilph, one of the Four Divine Generals of the mysterious Spiral King, arrives to support Viral's Enki, with the massive mobile Gunmen fortress, the Dai-Ganzan. Seizing the opportunity to land a great victory, Kamina and Simon pilot the Gurren-Lagann against seemingly overwhelming odds.

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Having temporarily stalled Viral and Thymilph in the last skirmish, the Team Gurren and their newly arrived allies join forces as "Team Dai-Gurren" and launch a decisive strike against the regrouping Gunmen force. The massive battle violently reaches its conclusion, but Kamina dies in the process.

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Team Dai-Gurren managed to take control of the enemy fortress, but is still mourning on Kamina's death, especially Simon. After falling off a cliff, he notices a Gunman throw a capsule into a deep valley. Simon inspects it and finds he is able to open it with the same drill key he uses to pilot Lagann, and inside is a young human girl named Nia, but their introduction is cut short when an enemy Gunman appears.

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Because Nia's identity was revealed, it confuses the team. Nia makes an effort to become familiar with them.

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Nia supports Simon who isn't yet recovered from the death of Kamina. Meanwhile, Guame is interested in Lagann and thinks of a plan in order to obtain it.

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Team Dai-Gurren go across the sea on the way to enemy capital, Teppelin. Adiane and Viral attack them from under the water.

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Nia wants to help the team out. Cytomander and Viral attack from the sky. Yoko decides to pilot Gurren because Rossiu is badly out of shape.

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One month has passed since the battle with Viral, and it's the sixth day of the battle for Teppelin. Guame and Cytomander with their troops confront Team Dai-Gurren.

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Teppelin begins to collapse. Also it begins the final battle against Lord Genome.

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The journey of Simon's boyhood.

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7 years have passed since the fall of Teppelin. A new capital named Kamina-city has been built, and the human advanced in civilization. However, Simon and Rossiu feel very anxious about Lord Genome's last words.

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The unknown enemy appears, and the human is confused. Simon is informed about an enemy from an unexpected person.

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Simon drove back an enemy. When he returned to Camina-city, he was arrested.

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Simon meets Viral again in the prison. Meanwhile, Rossiu pushes ahead a evacuation plan of the human, but the time left for them is really small.

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Yoko changed her name and she has lived quietly as a teacher of the elementary school.

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Arc-Gurren goes into space. But soon after, a large energy blast comes from the moon.

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Team Dai-Gurren keeps the Anti-Spirals attack off. Meanwhile, Rossiu goes to his home, Adai.

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The team aim at the mother planet of the Anti-Spirals beyond the dimensional wall.

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Anti-Spirals make an attack in waves against the team. The universe changes to high-density water, Super Galaxy Dai-Gurren starts to sink.

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Anti-Spiral shuts the mind of the crew members into a multiverse.

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The grand finale, with Simon, Yoko the mecha Tengen Toppa Gurren Lagann and all their crewmates fighting for their lives, as well as for their home planet, Earth, in the epic final battle against the Anti-Spiral.

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