GUP functionality must be managed via the SEPM, as it's the SEPM itself that compiles the list of available GUPs.
It sounds as if (perhaps) there have been some LU Policy changes going on? Can you confirm the below please?:
- There is a LU Settings policy that defines your intended GUP either as a Mulitple or Single GUP
- That this policy is assigned to the GUP (i.e. the group in which the GUP resides)
- That the policy serial number on the GUP and the SEPM match
Recently (since RU2 anyway) a common thing many admins miss is that listing a GUP in the Explicit GUP list alone does not enable GUP functionality (which is why checking to see it's in the Multiple/Single GUP list is the first point).
If all of the above are true, then I'd personally recommend checking out the globallist.xml file (found in the below location) to see if it's even in the list (by IP address):
<Program Files>\Symantec\Symantec Endpoint Protection Manager\data\outbox\agent\gup
If the points are all true and it's not in the list, then we'll need more in depth logs and stuff.