The episode opens with a short montage of clips from the series' twelve seasons, then segues to Sheldon and Amy, who are up late waiting for a call from the Nobel Committee. Following a prank call from Kripke, they are told they've won the Nobel Prize in Physics for their super-asymmetry work. The attention from the media and the university bothers Sheldon. Amy is saddened by an unflattering picture of her in a news report, so Raj convinces her to get a makeover. She loves her new look but Sheldon demands she change it back. Leonard calls him out for being rude, but Sheldon flees when he sees Penny emerge from the newly repaired elevator. Sheldon and Penny go to the Cheesecake Factory and Penny tells Sheldon that change is the only constant thing in life. On a TV, they see Bernadette and Howard take credit as Sheldon and Amy's best friends. Raj and Leonard defend Amy, with Leonard accidentally breaking Sheldon's DNA molecule model in Apartment 4A. Penny convinces Sheldon to ride in the elevator.
Sheldon's mother Mary refuses to attend his wedding unless he invites his older brother George, with whom he is no longer speaking. Sheldon and Leonard fly to Texas to talk to George, who now owns a chain of tire stores. He refuses to attend and later explains to Leonard and Sheldon that the family sacrificed a lot to fund Sheldon's education, and he was stuck caring for their mother and sister Missy after their father died while Sheldon was in college. Sheldon never thanked him for this. Leonard takes George back to the hotel room where Sheldon apologizes for what he did and the brothers reconcile. George agrees to attend the wedding. Meanwhile, Howard and Bernadette's children contract pinkeye, infecting everyone except Penny, much to Amy's fury.
Two nerdy physicists share an apartment and an unlikely friendship with their beautiful neighbor with whom one of them is infatuated. Like the universe after the big bang, the show's popularity expanded, thanks to breakout star Jim Parsons, along with the chemistry among the friends and the developing romance between Leonard and Penny. The addition of Melissa Rauch and Mayim Bialik in later seasons also enhanced the stories and relationships of the leads.
After Sheldon reminds the guys about the time they mined Bitcoin without him, the guys go on a quest to find their suddenly valuable missing cryptocurrency. They realize the currency is on a laptop which Leonard gave to Penny when they dating, which she then gave to her ex-boyfriend Zack. After Leonard and Penny go to Zack's apartment, he shows them a seven-year-old video that Penny recorded on the laptop soon after she broke up with Leonard. Leonard is touched by the video which shows a drunk Penny lamenting the break-up of her relationship with him.