Before introducing the weirdest TV family since Transparent's Pfeffermans, Tig Notaro's new Amazon series One Mississippi — which drops on Sept. 9 — opens with an almost Russian sense of loneliness. After reminiscing alone to an invisible radio audience about her childhood stuffed animal restaurant, Notaro shuffles painfully through an airport in clothes that clearly used to fit. They hang off her now as she visits one bathroom after another after another on her way to her gate. She's sick. She's survived breast cancer, recovered from a double mastectomy, endured chemotherapy and battled C. difficile, and she's traveling from Los Angeles to Mississippi to take her mother off life support (she tripped and fell in a freak accident and was pronounced brain dead).

The basic scenario will be familiar to most viewers thanks to Notaro's massively popular stand-up performance at Largo — the one that famously began with "Hello! I have cancer. Hello!" before spiraling out into one of the most bleakly hilarious sets in comedy history. One Mississippi makes good use of that meteoric rise, gesturing at Notaro's history in ways it would otherwise have to explain.

But there are differences: Notaro's theme back in 2012 was loneliness. Since then, she's starred in a Netflix documentary and an HBO special, gotten married, and become a parent to twins. Loneliness isn't her default terrain anymore, and the Amazon series registers that change. One Mississippi seamlessly develops Notaro's exhausted, bemused monologue — which covers illness, shock, bereavement, and a solitude so complete it finds its only expression onstage at the comedy club — into a family dramedy. Notaro's loneliness gives way here to some of the most tantalizingly specific family drama I've ever seen on television.

Notaro's long excremental journey lands her in Bay St. Lucille, Mississippi, where she grew up. And that's where things snap into a different focus. A "story DJ," Tig wants to dwell on her grief in all its precious and devastating singularity, but her losses are irritatingly communal. Her mother Caroline's death hit her brother Remy (Noah Harpster) and her stepfather Bill (John Rothman) just as hard.

This turns out to be the show's joy and its tension: Who can we feel with and who can we blame? The relationship between stepparents and stepchildren is never easy, and with Caroline gone, Tig, Remy, and Bill are forced to jumpstart a kind of internal audit of what they all mean to each other in her absence.

It's a fantastically rich premise. Rothman plays Bill as a tidy, structured, and dutiful pedant who — for love of his wife — tolerates living with his stepson Remy, an amiable, easygoing high school coach disinclined to finish anything he starts. Both Bill and Remy are kindly men. They mean well (both express real concern about Tig's health). But, despite their differences, they share a tendency to overlook the big stuff. For instance, they prioritize the cat's feeding schedule over sitting with Tig at the hospital while Caroline passes away.

It's worth highlighting some of the exceptional writing here (thanks to Notaro and co-creator Diablo Cody) as well as the acting: Rothman portrays Bill as someone clearly obsessed with order and cleanliness who strives to suppress those instincts to care for his stepchildren. He fails often. When Tig wonders whether her mother chose the flowers in a vase on the table, he confirms that she did. But before Tig has even a second to contemplate her mother's last bouquet, he observes that they'll need to get rid of them soon or bees might come into the house. "Maybe let a bee in from time to time, Bill," Notaro says in that trademark deadpan.

Something similar happens with the chair Caroline died in: Tig and her stepfather respond to it very differently, and it becomes a metaphor for something else entirely. What do you do with your dead mother's shirts?

What sticks with you as you're watching One Mississippi — thanks not just to the writing but also to Nicole Holofcener's direction — is how firmly the show subordinates its symbols to its character work. Notaro's illness comes up often, but if it sometimes gets an intelligently lyrical treatment, its symbolic function is always secondary to its biological function. Her body is real, and so is the toilet paper it goes through.

As for the few symbols that do arise, they keep slipping into their literal meanings. This is what death does: A chair is really just a chair. A stain should just be a stain. These things aren't there to gesture at some transcendent truth, but to index how characters are differently processing the physical and emotional dimensions of loss.

This is a show about clashing mourning styles among people who are very much each other's intimates; that those conversations are often so disappointing — that they're unable to see each other's symbols the same way — is what makes it so compelling (and yes, funny) to watch.