It has often been tempting, but never a safe wager, to predict the demise of Donald Trump.

He lost the presidency and both houses of Congress, and was impeached for high crimes and misdemeanors twice. He’s being investigated in New York for business fraud, and in Georgia for election fraud. He’s being probed by the House’s Jan. 6 select committee — and, one would hope, ultimately by the Justice Department — for whipping up a riot and attempting a self-coup.

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Yet somehow he has managed to survive, legally, financially and politically. Indeed, astonishingly, he remains far and away the leading candidate for the Republican presidential nomination in 2024.

But maybe, just maybe, this time will be different.

On Thursday, a judge in New York ordered Trump, along with his daughter Ivanka and his son Donald Jr., to testify within 21 days at civil depositions in the New York attorney general’s investigation of potential fraud at the Trump Organization. The judge’s opinion brutally rejected Trump’s arguments for blocking the depositions: It would have been “blatant dereliction of duty” for the attorney general not to take the testimony, the judge explained, because prosecutors have unearthed “copious evidence of possible financial fraud” in Trump’s business.

That evidence includes a letter that might turn out to be, as a practical matter, the biggest blow Trump has ever suffered, even bigger than his six corporate bankruptcies and two presidential impeachments. A blow dealt not by prosecutors, plaintiffs, politicos or the press — but by his own longtime accountants.

As the judge noted, and as revealed in court papers filed on Monday by the attorney general, Trump’s accounting firm, Mazars, sent a letter on Feb. 9 to the Trump Organization terminating its relationship with Trump. The letter was astounding in many respects.

Mazars said that 10 years of Trump’s financial statements, from 2011 to 2020, “should no longer be relied upon,” and that Trump should tell that to the people he gave them to. The accountants explained that they reached this conclusion based upon court filings previously made by the New York attorney general, as well as the accountants’ own investigation and other sources.

Dana Milbank: We need a ‘Mazars warning’ on everything Trump says

And then they quit. Under the “totality of the circumstances,” Mazars wrote, “we have also reached the point such that there is a non-waivable conflict of interest with the Trump Organization. As a result, we are not able to provide any new work product to the Trump Organization.” Oh, and by the way, Donald and Melania’s tax returns are due in four business days — but, hey, we promise “to facilitate a smooth transition to your new tax preparers.” Best regards, Mazars.

Translated from legal-accountingese, the letter was an unmitigated disaster for Trump, far beyond his possibly having to file late returns. By saying the statements “should no longer be relied upon,” the accountants effectively announced, You misled us. By “totality of the circumstances,” they likely meant, The prosecutors investigating you, and the case they’re making, are serious.

By pronouncing “a non-waivable conflict of interest,” they were all but saying, We’re on team A.G. — or we might have to join someday soon. And by saying no “new work product” and quitting, they essentially declared, We don’t trust you — and we’re certainly not going to jail for you.

All this could threaten Trump’s livelihood — his all-important mogulhood — in a way no setback ever has before. Even a guilty verdict in a Senate impeachment trial would have affected only his entitlement to temporary government housing. And when he ran into financial trouble in the 1980s and ’90s, he had legions of lawyers and accountants to help him work things out with the banks and the courts.

Now the man who long has had trouble finding decent legal representation might find it all but impossible to find new auditors and tax preparers. It’s hard to imagine that any reputable accounting firm will touch his tax returns, let alone fix and bless his financials for a decade or more.

Even if lenders don’t exercise any rights they might have to call in their loans, Trump apparently still needs to refinance hundreds of millions’ worth of them soon. As Trump biographer Timothy L. O’Brien of Bloomberg Opinion puts it, “Good luck refinancing your debt when the accountants” — who have just declared a decade of your financials utterly worthless — have “just walked out the door.”

So Trump would face a heap of problems even if the New York attorney general (and the Manhattan district attorney she’s working with) closed up shop tomorrow. No wonder Trump’s son Eric was all but crying when he mentioned the prosecutors this week on Fox News.

But as Thursday’s ruling makes clear, the prosecutors aren’t going away anytime soon. And in 21 days, absent some relief from a higher court, Trump will face a profound conundrum at his deposition.

Will he testify and (assuming he’s even capable of it) tell the truth, and possibly implicate himself in crimes? Or will he provably lie under oath, and virtually guarantee himself an indictment for perjury?

Or will he do the sensible thing — plead his Fifth Amendment right against self-incrimination hundreds of times, as Eric Trump and the company’s finance chief, Allen Weisselberg, already have done — and face the political embarrassment (and, in civil litigation, the negative inferences) that would entail? In court Thursday, Trump’s lawyer said that he was advising his client to do precisely that.

Stay tuned. Could this be, at long last, the beginning of the end for Trump?

As always, don’t bet on it — but this time, don’t be surprised if it is.