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Deputy Treasury Secretary Neal Wolin, who helped steer the US economy through the Great Recession and financial reforms, will step down next month, the Treasury Department on Tuesday.
Wolin, 51, has served more than four years in the administration of President Barack Obama.
He will step down at the end of August, the Treasury said in a statement.
The Treasury had previously announced Wolin would stay through a period of transition after Treasury Secretary Jacob Lew took office in late February.
Wolin had been acting Treasury secretary after Lew's predecessor, Timothy Geithner, departed in mid-January.
He was confirmed as deputy secretary in May 2009 and is the longest-serving deputy secretary in the department's history.
The White House has not signaled who will be nominated to replace him, but reportedly is considering candidates from the financial sector and the Federal Reserve.
"For more than four years, Neal has played a key role on my economic team," Obama said in the Treasury statement.
"His deep knowledge and excellent judgment helped us prevent a second Great Depression, pass tough new Wall Street reform, strengthen our financial system, foster growth here at home, and promote economic development around the world."
Wolin is planning to take a post with a think tank "as he mulls other options outside government," The Washington Post said.