Twilight wakes up one day to find that things are different. Everypony is gone, and there's a persistent sheet of fog dominating all of Ponyville. But that's the least of her worries. It only escalates from there.
(Featured on EqD) A dark and tragic event occurred some years ago in Ponyville, and it involved an equally dark and dysfunctional family. They are still discussed among us to this day.
Sombra's magic is slowly consuming all of Equestria, and the ponies need the help of the most unwilling human to survive. It is for his own sake as well.