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Inspired by the 12 zodiac animals of the East, Twelve tells the story of 12 angels living in the human world in human form to protect the Korean Peninsula from evil spirits. Long ago, the angels barely managed to seal the forces of evil in the gates of hell through their sacrifice, bringing peace. However, with the evil spirits awakening, chaos returns.
As angels clash with Samin's fallen angels, Taesan falls defending Mirr, only to rise again to seal away the evil and save the angels.
Ogwi prayed to God, but a different entity answers him. To stop Samin from stealing Mirr's dragon soul, Taesan storms an underground temple in fury.
O-gwi battles Sa-min for the soul stone and escapes with Mirr. Tae-san opens the Hellmouth, restoring the angels' powers but unleashing evil worldwide.
Tae-san protects the angels and Geum-soon, while Sa-min kidnaps Mirr. O-gwi takes the power of Mirr and the soul stone. Ma-rok unleashes his wand's power.
Ma-rok warns Tae-san of O-gwi and Sa-min's return. As they sense the evil at their gathering, Geum-soon, the only human Tae-san cares for, becomes a target.
After evil spirits strike, Tae-san worries for the injured angels. O-gwi, with the soul stone, vows revenge as Ma-rok secretly hunts Sa-min.
While Tae-san is haunted by his past guilt, Sa-min seeks O-gwi's help to steal Mirr's power. An odd light signals the evil's return.
Taesan and the angels live in disguise among humans. Samin discovers Ogwi, who has been sealed away.