The U.S. presidential election won't be the only consequential vote this year.

After negotiating more favorable terms to remain in the European Union, British Prime Minister David Cameron has slated a June 23 referendum on the United Kingdom's future with the 28-nation E.U. The vote's gravity is significant, if not seminal, for the U.K as well as the U.S. and the E.U. itself, as each would be weakened by a "Brexit" (British exit).

Among the compromises Cameron extracted are changes to social services benefits for non-British citizens, pledges to not discriminate against Britain's financial sector despite the U.K.'s not using the euro and an exemption from the E.U.'s treaty pledge to form an "ever closer union."

To some (including other European nations frustrated by Brussels), these are significant concessions. To others, especially within Britain, they are less consequential. But now that they have been granted, Cameron has a special responsibility to campaign as vigorously for continued E.U. membership as he did for his own re-election, which, after all, was predicated on the promise of an eventual referendum on E.U. membership.

"We are approaching one of the biggest decisions of our lifetimes," Cameron said in announcing the renegotiation and resulting referendum. "Leaving Europe would threaten our economic and national security."

Cameron is correct, and he could have added that a Brexit might impact the "special relationship" with the U.S., as well as Western cohesion in countering Russia aggression, Mideast chaos and other challenges.

"In geopolitical terms, it's inevitable that a British withdrawal from the E.U. would weaken Europe as an overall political power, and that is significant because of the transatlantic alliance and also because of the increasing threat posed by Russia," Eric Schwartz, dean of the University of Minnesota's Humphrey School of Public Affairs, told an editorial writer.

It's also an existential threat to the future of the U.K., which may not remain united if it splits from the E.U. Polls indicate widespread sentiment in Scotland to remain, and a "no" vote could rekindle the secessionist movement that in 2014 almost led to a U.K. breakup. Wales and Northern Ireland seem to favor closer ties to Europe, too. And U.K. dissolution would diminish Britain geopolitically just as the West needs to respond to global crises.

It could also spark demands for similar votes across the union just as beleaguered leaders like Angela Merkel face increasing pushback against refugee resettlement and economic lifelines to Greece.

While U.S. leaders usually refrain from weighing in on elections abroad, President Obama has correctly said that it is in America's best interest that the U.K. remains in the E.U. But, ultimately, it will be up to British leaders. Several of Cameron's cabinet leaders have broken with their prime minister, as has Boris Johnson, London's popular mayor (and Cameron's political rival). So now Cameron must make the case against an E.U. breakup that poses a significant risk at exactly the wrong time.