The story, also adapted into a live-action film, is told from the point of view of 14-year-old Eriko, who is left in charge of her younger brother Daigo, when her parents disappear. Contrary to most manga, in Route 225, the disappearing parents are a major part of the plot. Daigo and Eriko have somehow been transported to an alternate world, from which they are still somehow able to dial back cryptic messages to Earth mobile phones.

Route 225 is based upon the 2002 novel by Chiya Fujino.