The Oscar-winning actress will reunite with the Glee creator for the big-screen adaptation of the play of the same name, about the HIV-Aids crisis in New York in the early 1980s, reported Collider.
Julia, who worked with Ryan on Eat Pray Love, is set to play Dr Emma Brookner, a paraplegic physician who treats several of the earliest victims of the disease.
Mark Ruffalo is on board to portray Ned Weeks, who "witnesses first-hand the mysterious disease that has begun to claim the lives of many in his gay community and starts to seek answers", while Matt Bomer - who was previously seen in Magic Mike - plays Felix Turner, a reporter who becomes Ned's lover.
The Tony award-winning play, which debuted in Broadway in 1985, has been adapted for the screen by original screenwriter Larry Kramer.
Production on The Normal Heart is expected to begin later this year in New York, for a scheduled release in 2014.
"Ryan has assembled an extraordinary cast to bring Larry Kramer's landmark theatrical achievement to the screen for the first time."