I really think this episode it's going to be about the redemption of Katherine.
Dead's knocking on someone's door, everybody thinks Katherine's about to die and so does she and so she rewinds a little bit and relives her tragic 500 years of solitude as she shares them with some of the gang. Some of them out of pity, out of long lost feelings for her, out of empathy, out of hope, rally around her to try and comfort or make amends with her and her ruthless ways considering she's biting it. They will eventually find a way to keep her alive, or some extra "cure" side effect be revealed and she will live, but it will be a turning point for everyone, at least when it comes to Katherine, and for Kat herself. I fail to realize how are they gonna fit all the special guests plus the current cast in one big around Katherine, since there's been talks about there being a scene getting them all together, although that might be just a rumor and everybody will be there, though not at the same time (or just the current cast will be).
When it comes to the mythology reveal, I'm thinking it might be something about the phrasing Tessa and Silas always used to refer to the cure: "a cure for immortality". Like, how important the actual name is. Inmortality means that you cannot die, but it does not NECESSARILY mean that you won't live eternally. How? Well, it could mean that you can't be killed (talking about human ways, the special means to kill vampires aside) and it won't really affect your longevity permanently.
The cure has already proven to be able to mess up with vampires big time, BUT we should all keep in mind that it was not meant for vampires at all, but to restore whatever magic was injected into Silas and Amara/Tessa with the Original Immortality Spell/Elixir. SO, The First Immortals are not really vampires, vampires are a pervertion of that one original spell, used and adapted by Esther so the cure might work differently for vampires. Time's catching up with Katherine, but what happens when it finally gets to the 500 years she owes it? Does she DIE?
I think it might send her back to where it took her initially: vampirism. So when time does its thing, she WILL die, and then wake up as vampire. A brand new vampire most likely, as to reset things a little bit. And there would be a beautiful symmetry in this for she would be a vampire again but a brand new person, as we've been seeing her become more and more human over the season (in a metaphorical way as much as literal).
This would also mean something quite big for the plot and direction of the show. The cure works, but since it's not made to cure vampires but the First Immortals, it works differently, and it's only a temporary solution.
Kevin and Julie stated some time ago that early on in the days of planning the show they knew a cure would introduced some time during the run of the show but this could be with one of two possible purposes: either to have the characters come to terms with their reality and fully accept themselves as the creatures they are now (which has been done already last season, as Stefan and Elena accepted reality to move on from it accepting themselves, and Caroline and Damon admiting they're fine like that, proving they've already moved on) OR it could be the end of the journey of the gang as they've learned a lot about themselves being vampires and some, if not all, go back to being human at the end of the show, next year (assuming they don't decide to extend), to whatever resolution they reach.
In that last case, that the cure has been proven to be temporary at this point might lead to someone investigating and working on it to find a way to pervert it (just like the Original Immortality Spell was) so that it will work for vampires, which might be why we're being introduced to the world of vampire researchers. We might get to see a new breed of witches come to town since, let's be honest, Bonnie's not a witch anymore and the writers seem to think they REALLY need witches. That's where Katherine's backstory as part of Traveler family might come into play: it could be Travelers who keep coming to town, old relatives of Katherine and Nadia or simply part of the same culture. It's possible they would work with vampire researchers in the creation of the New Cure and this could get to our denoument.
And it will be all tied around Katherine's character, as it has been all since the begining of the series, which is awesome.
Side Note: Long, hardcore speculation. I hope it makes some sense.