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My hard drive is filling up.  I'm going to add a second and want to move the .PlayonLinx directory to it, without moving my entire home directory.  Is that possible?  What I've done with Steam (Linux version) is to go in and tell each of the games to move to /home/Games, which is where I'd be mounting the new drive.

wine (used by POL) need to run from the home directory

You can move your home to an other partition/disk if you want

according to this article https://forum.winehq.org/viewtopic.php?t=108, first response from vitamin, you can move your .wine directory anywhere you want, just update wineprefix.  So it would seem that you can do it.  I just don't know how to update wineprefix in playonlinux, or update playonlinux.

also fyi, I want the directory to be accessible to all users on my computer.  Why download the same game multiple times? 

I tried one but other account didn't work. I need to update permission after each installation. I don't remember if winprefix and pol_home are hardcoded, but you can try with symbolic link if you want ;)