Outlook clients unable to connect to Exchange / Windows user profile

Exchange 2010
Outlook 2010/2013
I've seen a dozen or so computers in the last few weeks with this problem. The user suddenly cannot connect to the Exchange server in Outlook. (Sorry, I don't have specific error messages for this part.)
If I try a repair on the Email account or try to create a new Mail profile, I get this error:
"The action cannot be completed. The connection to Microsoft Exchange is unavailable. Outlook must be online or connected to complete this action."
I have verified all Exchange and mail security settings. Outlook configuration is not the problem.
I tried deleting %appdata%\microsoft\outlook and %localappdata%\microsoft\outlook.
I tried a repair on Microsoft Office.
I tried creating a new Mail profile for a different email account.
The only thing that has fixed this problem is a completely new Windows user profile, which tells me there is something else broken in the user profile. Does anyone have any idea what it might be?
Blog /
Twitter

Hi,
Please try to access Exchange via OWA.
This issue may occur when the HKEY_CURRENT_USER\Software\Microsoft\Windows\CurrentVersion\Explorer\User Shell Folders registry key does not contain all of the required data. Specifically, these problems occur if the AppData string value is missing from this
registry key.
To resolve this issue, import the User Shell Folders registry key from a working Windows User Profile.
Steps to perform on a working computer
Start Registry Editor. Click Start , type regedit in the Search programs and files box, and then press Enter.
Locate and then select the following registry subkey: HKEY_CURRENT_USER\Software\Microsoft\Windows\CurrentVersion\Explorer\User Shell Folders
On the File menu, click Export.
Specify the name of the .reg file and then click Save.
Copy the .reg file to the computer exibiting this problem.
Close Registry Editor.
Steps to perform on the computer displaying the above error(s)
Start Registry Editor.
On the File menu click Import.
Locate and select the .reg file exported from the working computer.
Click Open.
Close Registry Editor.
Best Regards.

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