RUN follows Ruby Richardson, who walks away from her ordinary life in the suburbs to revisit her past with her college boyfriend, Billy Johnson, with whom she made a pact 17 years prior that if either one of them texted the word "RUN" and the other replied with the same, they would drop everything and meet in Grand Central Station and travel across America together.
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With the end of their journey approaching, Ruby and Billy consider their future together. Are they finally being honest with each other? Babe and Laurel are forced together as they follow a new lead.
Stranded in the middle of nowhere, Ruby and Billy argue about what to do next. Each affected by the other's desperation, the two must come together to confront their actions. Meanwhile, Laurel makes a gruesome discovery and receives an eventful visit from Detective Babe Cloud.
A dramatic detour finds Ruby and Billy in unknown territory as they're forced to make a life-changing decision. As Ruby tries to keep everything together and get back on course, she and an emotional Billy seek the help of an amiable local taxidermist, Laurel.
Back on the train, Ruby seeks guidance from a new friend and gets a wakeup call from home that leaves her shaken. Meanwhile, Billy continues to lie about Fiona, who raises the stakes to get what she wants.
Ruby and Billy decide to spend a day in Chicago before making any rash decisions about their next moves. As the two anxiously await check-in at a lavish hotel, Ruby meets an exciting woman at a department store, while Billy tries to handle a relentless Fiona. Later, Billy comes clean about what drove him to run.
During their first night aboard, Ruby's mind is consumed by sex, while Billy probes for personal details she's reluctant to give up. Comforted by the fact that her husband believes she's on a weeklong yoga retreat – and determined to make Billy jealous – Ruby brazenly connects with Derek, a stranger on the train. Meanwhile, Billy works to shake a persistent figure from his past.
On a regular Tuesday morning, Ruby Richardson is shaken out of her humdrum suburban life when she receives an urgent text that prompts her to fly to New York and board a cross-country train, where she reunites with college ex Billy Johnson. As their adventure begins, Ruby and Billy fight the tension that still exists between them while attempting to root out each other's secrets.