Misako is one of the major protagonists of Ninjago: Masters of Spinjitzu. She is an archaeologist and a close ally of the Ninja. She is Lloyd's mother, Garmadon's widowed wife, Wu's sister-in-law, and the First Spinjitzu Master's daughter-in-law. Following the return of the Stone Army, Misako reunited with Wu and met the Ninja, assisting them in their quest to battle the Overlord and Garmadon. After the Overlord possessed Garmadon, Lloyd fought against him in the final battle, seemingly destroying him while also purifying Garmadon of his evil. Misako and Lloyd then departed with Garmadon with the hope of rebuilding their lives.
Misako and Garmadon later settled in a monastery. When the Nindroid conflict began, Misako remained at the monastery while Garmadon and Lloyd set off to face the Overlord. After Zane's supposed demise, the Ninja and Garmadon set off to a mysterious island to find their lost friend, which went unknown to Misako and Wu. Misako attempted to establish contact with them until the Ninja returned along with the Elemental Masters. The new alliance fought Master Chen's army at the Corridor of Elders. In a bid to defeat them, Garmadon had himself banished to the Cursed Realm.
Due to Garmadon's banishment, Morro escaped the Cursed Realm and possessed Lloyd, setting off on a quest to claim the Realm Crystal. Misako accompanied Wu and the Ninja in an effort to save her son, and they eventually succeeded in doing so. Some time later, the Ninja were framed for crimes they didn't commit, leading Misako to be captured by the police. However, a deceptive djinn named Nadakhan trapped her in the Sword of Souls. Misako was later freed, and due to Jay's final wish, recent events were undone and she was never captured. Shortly after, Misako journeyed to the Dark Island to investigate reports of missing fishermen, and ended up uncovering a diabolical plot by Clouse.
On the Day of the Departed, Pythor set off to have revenge on Lloyd, leading him to confront Misako and her son at the Corridor of Elders, where they were commemorating Garmadon. Lloyd fought against Pythor before he decided to leave for his own sake.
After moving into the Temple of Airjitzu and Wu being attacked by Acronix, Misako personally nursed him before he was captured and was soon lost in time. She later went on a discreet search for him, not telling anyone, not even her own son before finding Wu as a baby, later being captured by the Sons of Garmadon. She reunited with Lloyd and witnessed them attempt to bring Garmadon back and were slightly successful.
Following the supposed demise of the original Ninja and Wu, Misako became part of her son and Nya's team, The Resistance before she was arrested during the raid on their base. Upon hearing the return of the original Ninja and Wu, this inspired her and others to break out and help them restrain the Colossus.
After Faith and Firstbourne crashed down onto the Monastery of Spinjitzu's grounds, Misako helped nurse Faith back to health.