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Stapleton said she stepped down to spend more time with her husband and their young daughter.
"While it has been an honor to help Gov. Palin and her family over the last few years, I am also honored to have this incredible opportunity to stay home with my precious miracle, Isabella," who is 2 years old, Stapleton told Politico.
"I have missed significant moments in her life, but I look forward with great happiness to celebrating milestones as well as mundane moments with her as I refocus my priorities. I also look forward to seeing my saint of a husband again, too!"
Stapleton, who worked with Palin for three years, became an especially close adviser as the then-governor rose to national prominence during the 2008 presidential campaign. She served as a strategist and one of the few people trusted to speak publicly on Palin's behalf.
"Meg has been deeply involved in all things Palin and instrumental in Sarah's many successes," GOP fundraiser Fred Malek told Politico.
Before joining Palin, Stapleton worked for the investment firm Thayer Capital Partners, for the Republican National Committee, and as a local television news reporter in New York, Pennsylvania, and Alaska.
She reportedly told Palin of her decision in an e-mail last week, but the resignation became official Wednesday, Stapleton's birthday.
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