Why do some users keep getting prompted to restart Outlook?

Scenario

You are using the Exclaimer Cloud Signature Update Agent, and you notice that one or more users keep getting the following prompt, despite having already restarted Outlook:

Reason

There are multiple possible causes for this issue:

1. There may be a Group Policy, third-party application or something similar which might be modifying the Outlook's settings and conflicting with the Exclaimer Cloud Signature Update Agent.
   
   The Exclaimer Cloud Signature Update Agent configures certain Outlook settings such as, default signatures, access to signature settings and SendPicturesWithDocument using the Registry. If any other policies or applications are also modifying these settings then this may cause these prompts to occur unexpectedly.
   
   We recommend - you disable any such policies to allow the Exclaimer Cloud Signature Update Agent to determine the correct value for the setting.
   
   
2. Multiple Outlook profiles or Outlook profiles exist with corrupt data.
   
   It may be possible that there is an issue with the Outlook profile, which is preventing the Exclaimer Cloud Signature Update Agent from correctly applying the signature settings to Outlook.
   
   To help troubleshoot this issue - remove any unnecessary Outlook profiles and recreate the main profile in Outlook. For more information, please see how you can re-create the Outlook Mail Profile?