En’s death sets the motion for many things in this series. It is clear that whoever the CrossEyes boss is, they are the one who killed him. At this point it is more likely that one is either Caiman/Aikawa or Ai, as the professor points out. Though it seems more than likely that the boss is Ai, given that we see him using En’s magic. We know that Ai was turned into a sorcerer by the professor. Still difficult to know. We can also see what is possibly Risu going after him, which would have you think that the boss is Caiman/Aikawa.
For Nikadiou En’s death is good for her because she is freed from that contract. As En is too big a figurehead for her to avoid. We know her magic is time, but what is most interesting is that she calls Asu Kawajira. We knew that Asu raised her, but if he never told Nikaidou her name, that makes it odd.
Furthermore, we don’t know what Nikaidou did initially, but it did cause Yakumo’s death, as he was dead. Did Nikaidou change the past so that Yakumo potentially lived? Or did she just avoid her foster home? It’s good Asu is there to help her, but at some point she needs to conquer her past rather than living in fear if she wants to catch up to Caiman.