EXCLUSIVE UPDATED: NBC‘s plan to revamp single-camera sophomore comedy Up All Night as a multi-camera sitcom has suffered a major blow. I’ve learned that series star Christina Applegate is leaving the Lorne Michaels-produced project, which is still being re-conceptualized and is yet to film any of the five episodes in front of a live audience that had been planned. “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,” Applegate said. “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.” NBC would not comment. Some sources say the network is still looking to proceed with the series and may be eyeing Friends alumna Lisa Kudrow as a potential replacement for Applegate, while others say the show is now dead. Meanwhile, Applegate is getting ready to reprise her role in the Anchorman sequel, which begins filming this month.

Applegate’s exit follows the recent departure of series creator/executive producer Emily Spivey as the show has experienced a lot of behind-the-scenes turnover since last May when original showrunner Jon Pollack left. He was replaced by Tucker Cawley who, in turn, was replaced by Linda Wallem when NBC decided to turn Up All Night into a multi-camera comedy after 11 softly rated episodes of Season 2. Along with the format switch, Up All Night is undergoing creative changes, including in the balance between family and workplace comedy, that have not been completely locked in yet.

At TCA last month, NBC Entertainment president Jennifer Salke indicated that the strength of the show’s all-star cast – Applegate, Will Arnett and Maya Rudolph — was key in the decision to keep it going. “We know that that talented cast of actors, they’re not growing on trees,” she said, calling the multi-camera revamp “a bit of an experiment” but “we think it’s really one worth taking.”

In its original incarnation, Up All Night was a family comedy about new parents played by Applegate and Arnett, which was inspired by Spivey’s real-life experiences of going back to work soon after giving birth. Applegate sparked at the concept as she too was a brand new mom when she signed on for the project. The workplace element was expanded and switched from a PR firm to an Oprah-like talk show when Rudolph was cast as Applegate’s boss, and there has been speculation that the series will shift even further in that direction when it becomes multi-camera.

Up All Night was a noble effort — an unfiltered look at parenthood with a top-notch cast, which received mostly positive renews when it launched in fall 2011. But it didn’t quite click with audiences and, after so many changes to the show and its team that have taken it so far from the original vision, maybe it is time to let go.