Kotaku reports that a voice over casting call has revealed some potentially major Portal 2 details. The casting call was discovered by a tipster on breakdownexpress.com, a website devoted to listing casting calls for various projects. The casting call, which requires a subscription to view), is for a major role in the sequel, described as someone who "Goes from sidekick to principal antagonist." We won't spoil more than that here. Those who aren't worried about spoilers can find more info after the break.
The role is that of Cave Johnson, the founder and former CEO of Aperture Science. We say former because he was already long dead at the beginning of Portal. There are some interesting (and speculative) implications here. As Cave Johnson is dead, it's possible that Portal 2 will be a prequel. Backing up this assertion, the character details listed suggest that we may see Cave Johnson's descent into madness. Of course, it's possible that the character could be a ghost (or even an artificial intelligence), but the casting details certainly seem to suggest a more corporeal presence, especially given that he apparently "Goes from sidekick to principal antagonist."
Then again, the Aperture Science Handheld Portal Device was not completed until after Johnson's death, so everything remains pure speculation at this point. Perhaps we'll get to help Johnson craft some shower curtains?
Follow the "Source" link for the complete casting details.