As the saying goes, you can pick your friends, but you can’t pick your family. But what happens when a family member is also a friend, albeit one who is as loving and magnetic as he is exasperating and inappropriate?

“A Real Pain,” writer-director-star Jesse Eisenberg’s loosely autobiographical, beautifully observed dramedy, takes an affecting look at this familial dynamic as mismatched cousins David (Eisenberg) and Benji (Kieran Culkin) travel to Poland to visit the childhood home of their beloved, recently deceased grandmother Dory, a Holocaust survivor.

The cousins’ journey — which starts with a guided Jewish heritage tour of Warsaw and Lublin, after which they splinter off to Dory’s rural birthplace — covers as much emotional territory as it does physical. Though the sightseeing may, at first, seem like a device to throw the estranged David and Benji together for a much needed if inevitably fraught reunion, Eisenberg deftly blends the story’s strands in darkly amusing, moving and combustible ways.

But it’s the creation of Benji that proves the film’s secret sauce; he’s one of the most vivid and compelling characters you’ll see onscreen this year. Culkin, in a career-best turn, tears into the role with a remarkable mix of exuberance and pathos.

A rudderless, sporadically volatile guy who hit bottom after his grandma’s death (and reacted in drastic form), the unfiltered Benji is also the life of the party: an F-bombing, rules-be-damned whirling dervish who can charm the pants off a TSA agent, blithely mail himself a brick of weed (to Poland, no less) or turn a sober photo op into a buoyant theatrical experience.

But at times, there’s a defensive, slightly cruel streak to his patter that can eclipse his better angels (of which there are many) and test the goodwill of those around him.

In this case, that mainly includes the earnest David, a digital ad salesman and devoted family man with controlled obsessive-compulsive disorder and a low threshold for embarrassment, the latter of which Benji repeatedly tests. Benji may think David is too tightly wound — and he may be — but so is Benji, just in different, less overt ways.

The cousins’ complementary natures may have bonded them in their youth, and a genuine and abiding love clearly remains. But as adult traveling companions, their longtime dynamic too often creates more stress than camaraderie. When, in one of the film’s many fine exchanges, David succinctly tells Benji, “You light up a room and then, like, s— on everything inside of it,” you wonder how long he’s been waiting to say that.

Also subjected to Benji’s highs and lows are the other members of the tour group: wistful divorcee Marcia (Jennifer Grey, a pleasure); Rwandan genocide survivor and Jewish convert Eloge (a poignant Kurt Egyiawan); middle-aged marrieds Mark (Daniel Oreskes) and Diane (Liza Sadovy); and their bookish guide James (Will Sharpe, in a lovely U-turn from his enigmatic role in “The White Lotus”), a British non-Jew fascinated by Jewish history.

Kurt Egyiawan, left, Will Sharpe, Kieran Culkin and Jesse Eisenberg in the movie “A Real Pain.”

(Searchlight Pictures)

The genial bunch can’t help but be drawn to the warmly ebullient Benji — Marcia, in particular, finds in him a ready ear — until he has some hairpin meltdown about Jews riding first-class on a Polish train (“Eighty years ago we would have been herded into the backs of these things like cattle”) or what he deems James’ invasive fact-sharing at a hallowed cemetery. He leaves the others stunned and David mortified until the storm cloud passes and he’s his jaunty, loquacious self again. But we can see the increasing chinks in Benji’s armor with each passing setback.

For all the vivid historical spots the tourists explore (enhanced by Michal Dymek’s vibrant cinematography), nothing proves as much of a gut-punch as the group’s visit to the Majdanek concentration camp on the outskirts of Lublin. With a hushed reverence (the film’s splendid, Chopin-heavy soundtrack goes pin-drop silent here), James escorts them through the stark, gruesome chambers of the compound, accompanied by the ghosts of its countless victims.

The sequence crystallizes James’ early-on warning that this would be a tour about pain and, although Eisenberg as a filmmaker doesn’t linger at the heartbreaking site, it has an outsized effect on the action, as well as on everyone’s emotions, especially Benji’s.

The cousins’ eventual arrival at the home Grandma Dory left behind to escape the Nazis is handled in a way that’s unsentimental yet also credible and thoroughly touching, with a gentle twist that nicely serves the arc of David and Benji’s roller-coaster relationship.

If you know (and now you do) that the humble house seen here is the same one Eisenberg’s great-aunt fled from in 1939, it adds an eerie touch of verisimilitude to the already resonant scene.

Although Culkin walks away with the film, Eisenberg gives one of his best, most heartfelt performances (his famously urgent speech pattern is largely intact) as a man who has come to appreciate life’s responsibilities but has maybe lost a piece of himself in the process. The restaurant scene in which David, in Benji’s brief absence, tearfully reveals a profound array of feelings about his troubled cousin to their concerned tour mates is a knockout.

In a step up from his feature writing-directing debut, 2022’s “When You Finish Saving the World,” Eisenberg furthers himself here as a distinctive voice, one with a keen visual sense, a masterful ability to juggle tones and an innate feel for timing and pacing.