Anti-social outcast Manny Ulysses gets into another explosive “accident" after attempting to build a rocket to find his father, Sebastian the astronaut, getting him and his family banished from Houston. Traumatized by his father leaving him when he was a child to go to space, Manny’s behavior has become increasingly erratic and unstable as a teenager. Even though everyone else thinks he’s dead, Manny has coordinates to his father’s last known location, believing he’s still alive. Manny and his family leave Texas and move back to his childhood home in the dazzling city of Hollywood II, California. He unwillingly promises his mother Oleana he will do his best to forget about his father and make new friends. Manny gets accepted into the only school left that will take him: Hollywood Walk High School, an elite charter school for so-called "Special" students. On his first day, he befriends the musically talented Bo Domingo. Unfortunately, they are picked on and ostracized by the other students-Manny is intelligent but too arrogant, and Bo is funny but tries way too hard to get people to like him.
Things take an insane turn when Manny and Bo uncover a shocking secret: the Principal has been replaced by a scummy alien bounty hunter named Kaizar from the planet Praetoria, who can shapeshift into human beings! Along with his cybernetic sidekick Kelly, Kaizar has been sent by his dear leader, Major Krak, on a sinister mission—to look for Manny in order to kill Manny’s father! They believe that Sebastian will bring about the destruction of the Praetorian Empire. Manny and Bo are now caught in a race against time trying to get to Sebastian first, all the while “Principal Flunkenhiney” attempts to steal the coordinates from them! If they don’t find Sebastian soon, nothing will stop Major Krak and the Praetorian invaders from coming to Earth and colonizing it! Meanwhile, agents from the shadowy organization known as Area 51 ½ lurk behind every corner of the city, tracking the movements of the aliens for their own nefarious purposes. It’s a high school drama, a science fiction adventure, and an interdimensional journey into the human psyche all wrapped up into one show. It’s insane, goofy, heart-breaking, funny, action packed, dramatic, and everything in-between. It’s Manny and Bo.
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