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After Three Finger, Saw Tooth and One Eye escape through the Glenville Sanatorium, the brothers, with the help of serial killer Maynard (Doug Bradley), start a murdering rampage nearby the city of thos Fairlake, Greenbrier County, West Virginia where they first murder news reporter Kaleen Webber.
Meanwhile, five friends: Billy (Simon Ginty), his girlfriend Cruz (Amy Lennox), Lita (Roxanne McKee), her boyfriend Gus (Paul Luebke) and Julian (Oliver Hoare) are on their way to Fairlake, West Virginia to celebrate the Mountain Man Festival on Halloween. Along the way, they almost run over Maynard, who attacks them. Billy, Gus and Julian attack Maynard out of self-defense, but are all apprehended along with Lita and Cruz by Sheriff Angela Carter (Camilla Arfwedson) and her partner Deputy Biggs (Kyle Redman Jones). While Sheriff Carter leaves to take them to the police station, the cannibals appear and kill Deputy Biggs.
After being locked up in the police station, Billy confesses to Sheriff Carter that he owns his friends' drugs, and he stays at the police station while they are free to go. Meanwhile, the cannibals drive to the city, killing a guard at the power plant, and shut down the town's electricity. The teens register at a motel to stay. On her way to visit Billy, Cruz is chased by Three-Finger, who kills her. After leaving the motel, Julian goes back to the police station, only to learn Cruz did not return.
At the motel, Gus and Lita make love, afterwards, Gus professes his love for Lita and asks her to marry him. She scoffs, telling him she is moving to New York, and needs some time alone to find herself. After Lita gets up to take a shower, the cannibals capture Gus when he answers the door. Lita is attacked too, but she manages to escape. The cannibals proceed to break Gus's legs, and then dump him in front of the Sheriff's office. Sheriff Carter attempts to save him, but the cannibals run over him with their pick-up truck, killing him. Sheriff Carter frees Billy, and gives him, Julian and prisoner Mose (Duncan Wisbey) shotguns after deputizing them.
The Sheriff manages to communicate with someone via shortwave town asking them to call for backup, but the man on the other end thinks the message is a joke. Lita manages to make it to the Sheriff's office, but is almost killed when Mose shoots through the door as she tries to open it. The Sheriff then warns Julian and Billy not to go looking for Cruz, but they ignore her warning and go in search of her anyway. They wander the streets and find Cruz's dead body; while trying to get the body to the Sheriff's office, they encounter the cannibals and are captured. The cannibals kill them both with a snow blower. Sheriff Carter then sends Mose to go search for the deputies, but he unknowingly runs over spikes in the road and crashes. He awakens to find himself captured by the cannibals and they burn him alive.
After hearing Mose's accident over the radio, Sheriff Carter tries to go for help but discovers her husband bound in a car and tries to help him. She discovers too late it is a trap and he dies, she is then knocked out and captured. After Sheriff Carter leaves, Maynard convinces Lita that if she released him, he would let her live. However, after releasing him, Maynard proceeds to stab Lita's eyes out and threatens to rape her. Maynard then leaves the jail to meet up with "his boys", and Lita stumbles out the opened door. Carter awakens in the jail cell with her hands tied to the ceiling and Maynard gives Carter the option of her death, which is to be burned alive by fire or from a shotgun with the trigger tied to her feet, which will go off if she steps down off to her feet. They then proceed to burn down the cell.
As her feet begin to burn, Carter eventually triggers the shotgun, killing herself. Lita is then seen walking down the road, unable to see, asking for help when a truck stops. As Lita climbs in the truck and thinks she is saved, the occupants are revealed to be the cannibals and Maynard. The film ends with Lita screaming in terror, as the tow truck drives away into the night.
- Doug Bradley as Maynard
- Camilla Arfwedson as Sheriff Angela Carter
- Simon Ginty as Billy
- Roxanne McKee as Lita
- Paul Luebke as Gus
- Oliver Hoare as Julian
- Kyle Redmond Jones as Deputy Kevin Biggs
- Amy Lennox as Cruz
- Duncan Wisbey as Mose
- Borislav Iliev as Three Finger
- George Karlukovski as Saw Tooth
- Radoslav Parvanov as One Eye
- Peter Brooke as Jason Carter
- Finn Jones as Teddy
- Andrew Bone as George
- Rosie Holden as Ginny
- Harry Anichkin as Doctor
- Velizar Peev as Night Watchman
- Emilia Klayn as Kaleen Webber
Wrong Turn 5: Bloodlines was released on DVD and Blu-ray on October 23, 2012 by Twentieth Century Fox Home Entertainment. The Blu-ray edition is a two-disc set which includes a Blu-ray disc of the feature film, as well as a DVD/Digital Copy disc. Since release, the film has recieved praise from Doug Bradley's performance but was negatively reviewed by critics.
A sixth film, Wrong Turn 6: Last Resort was released in 2014, two years later and was yet another prequel and is the latest sequel.