We don't know a lot about Mass Effect 5, other than the few details gleaned from cryptic teasers that BioWare has shared over the years. The one constant is Liara, but her appearance doesn't tell us much, either, as she's an Asari, who can live up to 1,000 years.
Concept art does hint that the Destroy ending is canon, as we see a Mass Relay under construction. This would mean that all Synthetic life has been wiped out across the galaxy, including the Reapers and Geth. In this ending, Shepard can be heard breathing if you have enough Galactic Readiness, potentially leaving the door open for their return.
Only... FemShep actor Jennifer Hale hasn't received a call from BioWare, so it seems unlikely that our intrepid Commander will appear in the next game (unless she's pulling an Andrew Garfield on us). But she's more than willing if asked, telling IGN that she "would be there before they finish the sentence."
"Everyone out there, the more you tell them what you want, maybe the likelier it is that it'll happen," Hale encouraged fans.
The other issue with a potential Shepard return is that Mass Effect 5 looks like it will tie...
