I'm a fair way in to PoE now, and I just found out that the door to the Endless Paths in the stronghold main hall is locked, with no way to open it that I can see. Also, the chair lady won't speak to me any more (she just has the red no clicky circle).
I thought it might have been connected to my manually resolving an attack of lurkers and shades, but my last save before that also has the door locked.