Isshin Saitō is Yakumo Saitō's maternal half-uncle, biologically the half-brother of Yakumo's mother, Azusa, through their shared mother. After Azusa attempted to strangle Yakumo and disappeared, Isshin became Yakumo's primary paternal figure, taking him into his care at the Buddhist temple where Isshin serves as a priest. He later adopted Nao Saitō, Yakumo's younger cousin who is deaf from birth. Biologically, Nao and Yakumo are paternal half-siblings through their father, Unkai Saitō, making Nao Yakumo's adoptive cousin.

Characterized by unwavering kindness and a calm demeanor deeply rooted in Buddhist principles, Isshin deliberately wears a red contact lens in one eye to mirror Yakumo's natural red left eye. This gesture aims to alleviate Yakumo's self-consciousness and sense of isolation stemming from his appearance and supernatural ability, exemplifying Isshin's empathy and dedication. Isshin also named Yakumo.

Beyond guardianship, Isshin provides emotional stability and guidance to both Yakumo and Nao. He teaches Nao to navigate her world without hearing, emphasizing inner peace and resilience. Despite knowing the atrocities committed by Yakumo's biological father—including the rape of Azusa that led to Yakumo's conception—Isshin manages his anger through Buddhist practice, maintaining a non-judgmental outlook. He openly welcomes Yakumo's friends into their lives.

Isshin dies toward the conclusion of the series. Honoring his compassionate legacy, Yakumo consents to donate Isshin's organs, saving the life of a young girl. Isshin's passing profoundly impacts Yakumo and Nao, leading to Nao's subsequent adoption by detective Kazutoshi Gotou and his wife Atsuko.