Christina Applegate as Reagan on 'Up All Night'. Credit: Trae Patton/NBC

Can a show still go on without its lead actress? Fans of Up All Night will soon find out, as Christina Applegate is leaving the series after just two seasons.

"It's been a great experience working on Up All Night, but the show has taken a different creative direction, and I decided it was best for me to move on to other endeavors," the actress says in a statement to Us Weekly. "Working with Lorne Michaels has been a dream come true, and I am grateful he brought me into his TV family. I will miss the cast, producers, and crew, and wish them the best always."

Up All Night, part of NBC's Thursday night comedy lineup, featured Applegate and Will Arnett as a hip married couple whose lives are turned upside-down when they unexpectedly have a kid. It was inspired by the real-life experiences of series creator Emily Spivey, who exited the show in early January, prior to the sitcom's planned revamp, which would have seen it switch to a three-camera format for upcoming episodes.

NBC had no statement regarding the future of the sitcom, but Applegate already has her next gig lined up. She's set to reprise her role as Veronica Corningstone in the upcoming Anchorman sequel with Will Ferrell. Kristin Wiig, Paul Rudd, and Steve Carell are also among the star-studded ensemble.

"So excited Kristen Wiig has joined our cast for Anchorman 2," Applegate tweeted on Feb. 4. "Going 2 b best movie ever made. Besides the best movies ever made."