Windows Server 2008 R2 - RDSH - Registry bloat with Samsung Universal Print Driver
Solution 1:
I had the exact same issue and can confirm it is fixed in the new version of Samsung Universal Print Driver 2 (2.50.5) . I was also running 2.50.2 and the key in question was using 275MB. Simply uninstalling the old version and installing the new version on the server (I did not update any client drivers) reduced the size of the key to 3MB. I also tried logging on and back off and can confirm it now deletes the keys when you log off, unlike before.
If you're curious, before it would not delete the keys. In a single user environment this isn't a problem but since the printers are named for the user and the session, it is an exponential problem (for a 20 user server like mine you generate up to 400 keys... and that's if you only have 1 printer per client)
edit: the new key is called usp01 instead of spe__
Solution 2:
HP has this exact same problem. The issue is that the driver is not very smart when it comes to multiple users connected to the same printer mapping at the same time and it keeps trying to reinstall itself for each user. We never figured out exactly how to fix this, but we came up with two workarounds:
Solution A (easy fix but is a total hack)
Set the Windows Installer service to disabled. Stops the problem dead in its tracks. The downside is obvious though. As soon as you need to do an install or run updates, you must turn the service back on and the registry will immediately begin swelling again.
Solution B (ugly fix but is stable and supported)
Enforce the Remote Desktop EasyPrint driver via Group Policy. This makes print jobs render on the clients instead of the server. The downside here is that you will then need to manually remove every user's printer connection from every printer on every server in the farm, and then delete the drivers. I hope you're good with scripting!