The US LGBT group called the thriller about a hitman forced to undergo gender reassignment surgery against his will "sensationalistic", according to The Hollywood Reporter.
Rodriguez is set to play a male assassin who falls into the clutches of a rogue surgeon, who transforms him into a woman.
He would later take revenge against his tormentor, played by Sigourney Weaver. Apparently, this storyline is considered too inappropriate by GLAAD.
"We haven't read the script, but it's disappointing to see film-makers turning what is a life-saving medical procedure for transgender people into a sensationalistic plot device," the organisation's director of programs for transgender media, Nick Adams, said.
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As media watchdog, GLAAD has criticized a lot of TV shows as well as praised them. One time, it lauded "Glee" for bringing more homosexual characters to the small screen but slammed the show for using the word "tranny" to describe cross-dressing character Dr. Frank-N-Furter in an episode about "The Rocky Horror Picture Show".
It also slammed such Hollywood films as "Ted 2", "The Wolf of Wall Street" and "Get Hard" for making jokes at the expense of LGBT.