Zero Two engages the creature in her FranXX, but it is heavily damaged in the skirmish and crashes near Hiro. She introduces herself by her codename Zero Two, which is known to belong to an infamous FranXX pilot known as the 'Partner Killer.' Before Hiro can digest the encounter, the Plantation is rocked by a sudden Klaxosaur attack.

Skipping out on his class' graduation ceremony, Hiro retreats to a forest lake, where he encounters a mysterious girl with two horns growing out of her head. Hiro, an aspiring FranXX pilot, has lost his motivation and self-confidence after failing an aptitude test. Bred for the sole purpose of piloting these machines, these children know nothing of the outside world and are only able to prove their existence by defending their race. Children raised here are trained to pilot giant mechas known as FranXX-the only weapons known to be effective against the Klaxosaurs-in boy-girl pairs. In the distant future, humanity has been driven to near-extinction by giant beasts known as Klaxosaurs, forcing the surviving humans to take refuge in massive fortress cities called Plantations. As Sakuta tries to help Mai through her predicament, his actions bring him into contact with more girls afflicted with the elusive disease.

Despite the getup, no one seems to notice her, and after confronting her, he realizes that she is another victim of Puberty Syndrome. With an air of unapproachability, she is well known throughout the school, but none dare interact with her-that is until Sakuta sees her wandering the library in a bunny girl costume.

Mai Sakurajima is a third-year high school student who gained fame in her youth as a child actress, but recently halted her promising career for reasons unknown to the public. However, high school student Sakuta Azusagawa knows from personal experience that it is very much real, and happens to be quite prevalent in his school. It is a rare disease which only affects teenagers, and its symptoms are so supernatural that hardly anyone recognizes it as a legitimate occurrence. The rare and inexplicable Puberty Syndrome is thought of as a myth.

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