Isshiki Ōtsutsuki is the overarching antagonist of Boruto: Naruto Next Generations. He is an Ōtsutsuki clan member who is currently in possession of Jigen. According to Sasuke, Isshiki is the fourth Ōtsutsuki in a temple along with Kaguya Ōtsutsuki, Kinshiki Ōtsutsuki, and Momoshiki Ōtsutsuki. It is speculated by Sasuke that Isshiki is likely paired with Kaguya Ōtsutsuki.
In his brief appearance, Isshiki reveals to be cruel and obsessed with trying to retrieve the vessel for his own purposes. Isshiki shows little respect for the vessel he inhabits by stating that he is weak for him. Having deemed Jigen's body as weak, Isshiki is interested in using Kawaki as a vessel. Isshiki demonstrates a level of lenience when he had Naruto Uzumaki sealed away for further use in the future than to kill him despite the latter's insults, with the likely purpose of either extracting the Nine-Tails or using him as leverage to make Kawaki cooperate with him. Along with that, he openly noted that Sasuke was welcome to escape by himself if he could leave Naruto behind.
Currently the most powerful entity ever seen thus far, surpassing even Kaguya Otsutsuki, Isshiki's power is great enough for him to make light work of both Naruto and Sasuke at once.
Not much is known about Isshiki's past, but he was stated to be paired with Kaguya Ōtsutsuki. The two arrived on Earth but they split up. Kaguya ends up getting sealed away by her sons, while Isshiki remains on Earth for many centuries without being detected. At some point in time, Isshiki takes possession of Jigen and uses him as one of his vessel for his own purposes.
With the missing vessel, Kawaki, Jigen tasks Kara with going after and retrieve him. At one point, Jigen express interest when he hears that Boruto has a kama seal from Delta and thinks of Momoshiki and his plans. Jigen visits the Ten-Tails in an alternate space-time and tells it that he is not ready to be eaten by it. Jigen manages to absorb a lot of chakra taking on the form of Isshiki briefly. He later visits the Hidden Leaf Village where he tried to retrieve Kawaki but was unsuccessful and instead encounters and fights Naruto, the Seventh Hokage. Jigen and Naruto goes to another dimension where they fight until Sasuke appears. The two fight against Jigen until he manages to overwhelm them but since the latter expend so much chakra, it awakens Isshiki's personality. Going forth, Isshiki states that Jigen's body is too weak to contain his own power. Despite that, Isshiki in possession of Jigen incapacitates Naruto and Sasuke with his powers. Jigen prepares to kill Sasuke but the latter left as Naruto tells him to go. Jigen proceeds to seal away Naruto and the Nine-Tails. Jigen expresses interest in retrieving the Nine-Tails for himself. Jigen left Naruto sealed away as Isshiki, himself, states how weak of a vessel Jigen is.
- It is possible that Isshiki succeeded in taking over Kawaki, as the latter would fight with Boruto and express a lack of care for Naruto's fate, even gloating on how he had banished Naruto, seeming to indicate Isshiki had in fact possessed Kawaki and Naruto remains trapped in his dimension, with his fate after being seemingly trapped for so long without sustenance unknown.