Their relationship is deeply rooted not only in the emotion of their current lives, but in the memory of the father she lost and the brother he has tried to stand in for since 1963.
And the senator's effort to get Caroline Kennedy appointed to Secretary of State-designate Hillary Rodham Clinton's New York Senate seat is about more than the two of them: It's a chance to perpetuate a family legacy begun when President John F. Kennedy was first elected to the Senate in 1952.
"The Kennedys are tribal; there has been a Kennedy important in American politics now for more than a half-century," said Boston College political science professor Marc Landy. "So, the idea you could prolong that for another generation - if not more - is more than important. It speaks to their tribal instincts."
Edward Kennedy still occupies his brother's desk at the rear of the Senate chamber, although his tenure as the second-longest-serving member entitles him to something in the front row. He's also founding an institute in Boston to study the Senate and teach new senators its customs that will lie in the shadow of his assassinated brother's presidential library.
Caroline Kennedy, New York Attorney General Andrew Cuomo and many other Democrats have been mentioned as potential appointees to Clinton's seat. Kennedy has spoken to the man who will do the appointing - New York Gov. David Paterson - and New York City Mayor Michael Bloomberg gave her a boost Monday, saying "Caroline Kennedy can do anything."
A poll released Tuesday showed Kennedy and Cuomo to be the top picks of New Yorkers; each is favored by about 25 percent of those surveyed. The Marist Poll of 503 registered voters conducted Monday has a margin of error just over 4 percentage points.
Kennedy's interest in the job came as a surprise to some, given the former first daughter's longtime aversion to the public spotlight.
While everyone knew of her early years living in the White House with her father, mother Jacqueline, brother John Jr. and pony Macaroni, the family retreated from public view after President Kennedy's assassination.
The Kennedys blended into the masses in New York City, and the public came to know only the broad brush strokes of Caroline's life: college at Harvard, law school at Columbia, marriage to an older man, Edward Schlossberg, and then three children.
She popped up occasionally and mostly in connection with maintaining her father's memory, as she has done each year by presenting the Profiles in Courage awards at the John F. Kennedy Presidential Library & Museum in Boston.
On other occasions, such as the death of her brother in a plane crash, she has had to bear her private pain in public. Her friends have been valued in part for their discretion, explaining why little is known of her daily life and personal affairs.
Yet as her children have grown, the now-51-year-old Caroline Kennedy has steadily surrendered more and more of her privacy.
Books on civil liberties were followed by a job as advocate and fundraiser for New York's public schools. When she turned 50, she served as cover girl on the AARP's magazine - a shock to those who remembered her in pigtails.
And then this year came a watershed moment: Her announcement - with "Uncle Teddy" by her side - that she was endorsing Democrat Barack Obama for president.
"Over the years, I've been deeply moved by the people who've told me they wish they could feel inspired and hopeful about America the way people did when my father was president," she said in January at American University in Washington, where her father delivered a 1963 commencement address focused on world peace.
"This longing is even more profound today. Fortunately, there is one candidate who offers that same sense of hope and inspiration."
Later in the year, she served as co-chair of Obama's vice presidential search committee. Her partner in that task, Eric Holder, has since been nominated to be attorney general. Now, with her children between 15 and 20, Caroline Kennedy appears ready to become a political figure herself.
"She spent a lot of her life balancing public service with obligations to her family," her cousin Robert F. Kennedy Jr. told The Associated Press last week. "Now her children are grown, and she is ready to move onto a bigger stage."
A confidant of Edward Kennedy says the senator has been working the phones in recent days, trying to build support for his niece's appointment. Among those he has targeted: Sens. Charles Schumer of New York and Robert Menendez of New Jersey, the outgoing and incoming chairmen of the Senate Democrats' re-election committee.
The pitch? That Caroline Kennedy has the fundraising power not only to defend the seat in a required 2010 special election, but in 2012, when Clinton's term would end.
Kennedy spokesman Anthony Coley denied any strong-arming, saying, "Senator Kennedy has not contacted anyone in New York regarding the possibility of Caroline Kennedy serving in the Senate."
While some have noted the symmetry of Caroline Kennedy holding the Senate seat once occupied by her late uncle, Robert F. Kennedy, she has always been closest to Edward Kennedy's side of the family.
She interned in Edward Kennedy's Senate office after graduating from college. And he, the family patriarch, gave her away at her 1986 wedding. The two also stand side-by-side each year to give the Profiles in Courage political bravery awards.
In May, Caroline Kennedy was quick to Massachusetts General Hospital when the senator had a seizure; he was soon diagnosed with brain cancer. She also was there in July when he returned to the Senate chamber for the first time.
Now, in the twilight of Edward Kennedy's career, Caroline Kennedy may join him in the institution where he has served for more than 45 years.
And Edward Kennedy may have the chance not just to teach his Senate lessons to a newcomer, as he did with Clinton when she was first elected in 2000, but to return his brother's desk to his daughter.
