|“||No, Sam, it doesn't matter. (...) What I've been saying for months.(...) Ever since what?! We lost pretty much everyone we ever cared about? Ever since the Mark made Cass go crazy? Ever since I had to bury him in a Ma'lak Box? Ever since then?! Yeah! You know why? Because the monsters, they're everywhere! Everywhere! What we do, its not even hunting anymore. It's whack-a-mole. We don't even save people. Every friend we've ever had is either dead, or they got wise and they packed it in. (...) We lost, brother. We lost. I'm done.||”|
Using the spell given to them by Michael, the Winchesters and Castiel were able to lock God away. Castiel chose to take on the Mark of Cain created by the spell and bore the burden of trapping God. On April 17, 2020, while Sam, Dean, Castiel and Eileen were about to enjoy a movie night, they received a call from Jody that a vampire hunt had gone wrong, leaving Claire dead.
At some point between April 17 and January 6 of the next year, Castiel went crazy from the effects of the Mark. Dean was ultimately forced to lock his best friend in a Ma'lak Box and bury him, something that devastated Dean to have to do.
By January 6, 2021, the world had taken a turn for the worst with the Winchesters having recently been unable to save a bunch of victims from werewolves. Dean insisted that there was nothing they could've done as the place had been "crawling with wolves" and they had to wait, but Sam insisted that because they waited, the victims all bled out on the floor. Though Castiel could've healed them, Dean had been forced to lock his best friend away in a Ma'lak Box so he couldn't help them.
This timeline and version of Castiel was erased from existence after Sam chose not to trap God based on what he saw.