I've been playing Risen for a week or two without any issues or bugs until tonight. When I go to launch Risen from the Autostarter/launcher I can't click on "Play", it's completely grayed out. Up until today I've been launching Risen that way with no issues. I can still launch the game through the start menu. Nothing major on my laptop has changed in the past day (since the last time I was able to launch Risen through the Autostarter/launcher).

Any ideas of what could be wrong and how to fix it?

Hmm, not really, but I'd try starting the Autostarter/launcher explicitly as Administrator (right-click => Run as ..) to see if that makes a difference.

Thanks for the suggestion, but it didn't change anything. This problem is a real head-scratcher!

:-/ Maybe your anti-virus or Window's Data Execution Prevention is messing with the game. You could deactivate the former and add the game to DEP's exception list.

Another solution would be to copy the start menu shortcut to the desktop since that one is working.

In yet of another case of a Piranha Bytes game being weird, the Autostarter is working again, the only thing I've done is, well, nothing besides turning my laptop on and off a few times in the past couple of days.

As long as it works ;-D

Indeed!