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| Antonio Banderas | Gregorio Cortez |
| Carla Gugino | Ingrid Cortez |
| Alexa Vega | Carmen Cortez |
| Daryl Sabara | Juni Cortez |
| Steve Buscemi | Romero |
| Mike Judge | Donnagon Giggles |
| Danny Trejo | Machete Cortez |
| Cheech Marin | Felix Gumm |
| Emily Osment | Gerti Giggles |
| Ricardo Montalban | Grandfather |
| Holland Taylor | Grandmother |
| Alan Cumming | Fegan Floop |
| Taylor Momsen | Alexandra |
| Christopher McDonald | President of the USA |
| Bill Paxton | Dinky Winks |
| Tony Shalhoub | Alexander Minion |
A young sister and brother encounter mutants and a wild scientist while searching for a device that could destroy Earth.
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