TV-Series
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Seishirō Sakurazuka, heir to the Sakurazukamori assassin lineage, gained the title by killing his mother Setsuka. She prophesied his death at the hands of someone he loved.

In Tokyo Babylon, he maintains a veterinary practice in Shinjuku as cover. A chance encounter orchestrated by Subaru Sumeragi's shikigami initiates contact. Seishirō professes romantic interest in Subaru, secretly fulfilling a childhood bet: after young Subaru witnessed an assassination, Seishirō spared him on the condition that if they met again, Seishirō would spend one year pretending to love him. Should Seishirō develop genuine feelings distinguishing Subaru from "objects most people treat like trash," he would spare Subaru's life. After a year of apparent courtship, during which Seishirō sacrificed his right eye protecting Subaru, he declares the bet lost due to his inability to feel genuine emotion. He attempts to kill Subaru but is thwarted by Subaru's grandmother, who is crippled.

Following this, Subaru's twin sister Hokuto confronts Seishirō, aware of his nature. She offers her life for Subaru's safety. Seishirō accepts and kills Hokuto, though she casts a final spell ensuring that if Seishirō ever attempts to kill Subaru the same way, the death reverses onto himself.

Years later in X/1999, Seishirō resurfaces as a Dragon of Earth aligned with forces seeking humanity's destruction. He battles Subaru, now a Dragon of Heaven. Their conflict culminates at Tokyo's Rainbow Bridge. Seishirō moves to kill Subaru with the same chest-piercing technique used on Hokuto. Hokuto's spell activates, reversing the attack and causing Seishirō's death by Subaru's hand. This outcome is interpreted as Seishirō's deliberate suicide, fulfilling his wish to die by Subaru's hand and his mother's prophecy. After his death, Fuma Monou gifts Seishirō's remaining eye to Subaru, completing a ritual that transforms Subaru into the next Sakurazukamori and a Dragon of Earth.

In Tsubasa: Reservoir Chronicle, an alternate Seishirō appears as a dimension-traveling treasure hunter. He trades his right eye to the witch Yūko Ichihara for interdimensional travel abilities to seek vampire twins named Subaru and Kamui. He mentors Syaoran Li in combat and wields a magical feather capable of summoning and controlling oni. His quest concludes alongside his brother Fūma and the vampire twins in an ambiguous alliance.

Seishirō's abilities center on advanced onmyōdō, specializing in shikigami manipulation and intricate illusions. His Sakurazukamori techniques involve lethal applications of spiritual energy, often manifesting through cherry blossom motifs.

The live-action film Tokyo Babylon 1999 depicts Seishirō with minor alterations: he magically strangles victims instead of using his signature chest-piercing technique. In this continuity, Hokuto's spirit possesses a potential victim and brokers peace between Seishirō and Subaru, averting their cycle of vengeance.