In case anyone else runs into this issue, while I didn’t find the cause, I was able to find a solution.
What worked for me was: creating the IK Rig and retargeting the mannequin skeleton to the custom character skeleton (although it is the same as the mannequin simple), baking out the retargeted animations from the Manny Anim Blueprint, force locking the root on the rotated animations (in my case, this was walk forward and land), and then creating a new blendspace for the walk/run using the retargeted animations and a new anime blueprint.
It’s important NOT to duplicate the Manny Walk/Run Blendspace and Animation Blueprint and then plug the new animations into it. While I couldn’t figure out where this was, something in those causes the root to rotate during blending, so even with retargeted animations, my character was rotating forward 90 degrees whenever he changed direction during Play in Editor.
It would still be cool if someone was able to find the root cause (no pun intended), but I hope this workaround helps!