The five-time Emmy winner is following a succession of notable guest stints -- on "Rescue Me" (for which he earned his most recent Emmy), "Curb Your Enthusiasm" and "The Good Wife" -- by getting back into the series game full time.
Premiering Thursday NBC's "The Michael J. Fox Show" casts him as Mike Henry, a New York television reporter who has Fox's Parkinson's disease and resumes his job after five years off.
Mike's return to the workforce is applauded by his wife, (Betsy Brandt, "Breaking Bad") and children, particularly the daughter (Juliette Goglia) who's documenting the situation on video for a school project.
"I knew that it was not anything to take lightly, and I really thought about it a lot," said "Family Ties" and "Spin City" alum Fox of tackling weekly work again.
"It was a combination of my experience on 'The Good Wife' and just thinking that the risks involved for the network were counterbalanced by the fact that I was a familiar quantity and that maybe people out there were ready to watch something I would do.
Though it surely is not a humorous subject, Parkinson's is woven into the humor of "The Michael J. Fox Show" through the main character's experiences.
The opening half-hour flashes back to a "chair incident" on the WNBC-TV news set that factored into the fictional Mike's time off, and it also shows his mishaps in making an accidental 911 call and trying to serve his family breakfast.
"We wanted to set it up and deal with it, then just gradually let it come up in organic ways throughout the rest of the run of the show," Fox said.
Fox's new co-stars also include two-time Tony Award winner Katie Finneran ("Promises, Promises," "Noises Off") as his sister, and Wendell Pierce ("The Wire") as his boss.
Real-life wife Tracy Pollan -- whom Fox famously met on "Family Ties" when she played girlfriend Ellen to his Alex P. Keaton -- guests in a second episode airing on the show's premiere night as a neighbor that Fox becomes interested in.
Fox said he found it "really cool" to work with her while also acting with someone else portraying his spouse.
"The Michael J. Fox Show" airs at 9 p.m. Thursday on NBC with an hourlong special premiere of episodes 1 and 2.
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