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When Professor Pippy P. Poopypants comes to Jerome Horwitz Elementary School to teach science, and he goes off the deep end because students make fun of his name, only Captain Underpants can save the school from the professor's perilous plot.

Luke, disgruntled that his brother and friend have become superheroes, fails at solving crimes alone but when he discovers an alien plot to overthrow the world, only his sworn enemy will listen.