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Five years after giving up his powers and separating from his friends, Leo San Juan has started a new life trying to focus on his family and their bakery, staying away from danger and adventures. However, Leo knows that his plans are rarely fulfilled and this time is no exception: while traveling with Nando to Veracruz, things start to get weird, and from the depths of the Tuxtlas jungle, an ancient curse has returned and only Leo can face it.
In the Mexican state of Michoacán, Dr. Jose Mireles, a small-town physician known as "El Doctor," shepherds a citizen uprising against the Knights Templar, the violent drug cartel that has wreaked havoc on the region for years. Meanwhile, in Arizona's Altar Valley—a narrow, 52-mile-long desert corridor known as Cocaine Alley—Tim "Nailer" Foley, an American veteran, heads a small paramilitary group called Arizona Border Recon, whose goal is to halt Mexico’s drug wars from seeping across our border.