Kiriko Endo is a pivotal character in the narrative of 20th Century Boys, primarily known as the older sister of protagonist Kenji Endo and the biological mother of Kanna Endo. Her role in the story is deeply intertwined with the central conflict, as her scientific expertise is forcibly exploited by the antagonist, Friend.

From a young age, Kiriko demonstrated a powerful intellect and a strong passion for biology and the study of microorganisms. This passion, however, becomes the source of immense tragedy and guilt. Friend, seeking to create a world-ending virus as part of his plan for global domination and subsequent "salvation," manipulated events to gain control over Kiriko. This manipulation involved the orchestrated death of her beloved, Moroboshi, which allowed Friend to position himself as her husband and the father of her child, Kanna. Against her will, Kiriko was coerced into creating the deadly virus that Friend intended to use to annihilate humanity.

Kiriko's personality is defined by a profound sense of responsibility and justice. She is portrayed as a "bad ass strong woman" who is deeply affected by the catastrophic consequences of her forced labor. Consumed by guilt over her role, she secretly developed the vaccine to counteract the very virus she was made to create. Her moral compass compels her to resist, and upon discovering the true, horrifying extent of Friend's cult-like organization, she took decisive action. She gathered evidence against him and entrusted it to the police, while also leaving her daughter, Kanna, in the care of her brother Kenji and their mother, before disappearing from their lives to pursue her own fight against Friend's plans. This act of leaving Kanna is a source of family tension, particularly with her mother, who views it as an abandonment.

Throughout most of the main narrative, Kiriko exists as a shadowy figure, seen largely in flashbacks. Her absence is a driving force for her brother Kenji, who raises Kanna. However, she continues to work in secret to atone for her past. She allied herself with the scientist Yamane, who was also involved in the virus's creation, convincing him of Friend's true intentions. Together, they worked to counteract the threat, with Kiriko focusing her efforts on developing a vaccine. In a final act of desperation and courage during the Friend era, Kiriko exposed herself to the next generation of the virus to test her own vaccine, which proved successful.

Her key relationships shape her entire arc. Her bond with her brother Kenji was significant, as she was a supportive and maternal figure to him in their youth, even buying him his first electric guitar. Her relationship with her daughter Kanna is marked by a long and painful separation, driven by Kiriko's mission to protect her from Friend. After the final defeat of Friend, Kiriko finds a measure of peace. She is last seen working as a volunteer doctor in Africa, dedicating her medical knowledge to helping the sick, where she is eventually reunited with her now-grown daughter Kanna and her aging mother. Her most notable ability is her genius-level intellect and specialized knowledge in microbiology and virology, which she uses both to create a devastating weapon under duress and, ultimately, to save humanity from it.