Elizabeth Warren has decided on a new crusade: Taking on President Barack Obama's ambitious trade agenda.
The Massachusetts senator, a powerful icon of the progressive movement, told me this week that she believes the Trans-Pacific Partnership, as currently drafted, could give multinational corporations a way around U.S. regulations they don't like and the ability to win judgments funded by U.S. taxpayers in an unaccountable international arbitration forum.
"This deal would give protections to international corporations that are not available to United States environmental and labor groups," Warren said. "Multinational corporations are increasingly realizing this is an opportunity to gut U.S. regulations they don't like."
The issue at play here, the investor-state dispute settlement process (ISDS), is eye-glazingly obscure. But Warren has proven before that she can take an issue like this and rally support in ways that gives the White House fits.
Read More What the Rudy, Homeland Security flaps say about GOP
She did it over Obama's pick of Wall Street banker Antonio Weiss for a senior Treasury Department post and the administration fears she could do it again over trade. The Asia trade deal, featuring a dozen nations including Australia, Japan, Singapore and Vietnam, is a centerpiece of Obama's second-term agenda and one of the few areas of agreement between the White House and congressional Republicans.
It is also a top agenda item for big business groups counting on better access to new markets and a stronger set of trading rules. Administration officials strongly dispute all of Warren's points, saying the U.S. is already party to 50 trade deals including the ISDS process and has never lost a case challenging a U.S. regulation or law.
White House National Economic Council Director Jeffrey Zients wrote on Thursday that the ISDS portion of TPP would only protect U.S. companies operating in markets with less developed legal systems and would not undermine U.S. laws.
"The purpose of investment provisions in our trade agreements is to provide American individuals and businesses who do business abroad with the same protections we provide to domestic and foreign investors alike in the United States," Zients wrote. "ISDS does not undermine U.S. sovereignty, change U.S. law, nor grant any new substantive rights to multinational companies."
Warren told me that she doesn't care that the U.S. has not lost a case yet. She fears that that pattern could soon change as big companies realize they can take the U.S. to court before an ISDS panel over wage, environmental or other rules they don't like.
Read MoreFear & loathing of Rand Paul's 'bash the Fed' stance
It's not clear that Warren will be able to knock TPP off course. Administration officials note that she has always opposed the deal as do many labor and environmental groups that are big Warren supporters.
The playbook has always been to first get trade promotion authority with mostly Republican support in the Senate and House and then use that to help finish off TPP and send it to Congress for an up or down vote.
But the question is whether Warren can peel off more on-the-fence Democrats in the Senate while also appealing to more populist Republicans wary of allowing a global court to make decisions on U.S. laws.
In a Washington Post op-ed on the subject, Warren made the case to Republicans to oppose TPP: "Conservatives who believe in U.S. sovereignty should be outraged that ISDS would shift power from American courts, whose authority is derived from our Constitution, to unaccountable international tribunals," she wrote. "Libertarians should be offended that ISDS effectively would offer a free taxpayer subsidy to countries with weak legal systems."
The administration is hoping none of Warren's arguments over ISDS catch fire because there is no chance of removing the language from TPP. But they also hoped she would not be able to rally progressives to block Weiss' nomination. This time could be different—there is a lot of big money behind getting trade deals done—but underestimating Warren's power is always a mistake.
—By Ben White. White is Politico's chief economic correspondent and a CNBC contributor. He also authors the daily tip sheet Politico Morning Money [politico.com/morningmoney]. Follow him on Twitter @morningmoneyben.