“IS” stands for “intersexual,” a term referring to people who cannot clearly be classified as male or female, and who may biologically possess characteristics of both sexes. Rokuhana's manga primarily deals with the troubles faced by the young Hoshino Haru (played by Fukuda), an intersexual who was registered as a girl at birth but has been raised as a boy.

Goriki plays Aihara Miwako, a mysterious classmate who tries to get close to Haru. Inoue Masahiro has been cast as Ibuki Kenji, a member of the soccer club whom Haru begins having feelings for. Nishida Naomi and Minami Kaho play Miwako's and Haru's mothers, respectively.