Symptoms

When doing anything K2 related on a SharePoint Site, like opening the K2 app to run the Registration Wizard, or clicking the K2 button on the Ribbon Bar, then you'll receive a 401 error.
 

Diagnoses

This started happening after a Cumulative Update for SharePoint 2013 was installed, specifically the April 2016 CU.

We also found that a new Security Certificate was installed on the SharePoint server and placed in the Trusted Root Authority for both the K2 and SharePoint servers.

 

Resolution

Since it seems that high-trust between the K2 and SharePoint servers has been lost, we had to re-run the AppDeployment.exe on the SharePoint 2013 server to regenerate the high-trust between K2 and SharePoint.

This was a once-off situation that only happened because of the change of Security Certificate, usually when updating SharePoint with a new Cumulative Update (or CU) this shouldn't happen. Please also be aware of the K2 Support Matrix and make sure which CU's are supported with which version of K2, here: http://help.k2.com/blackpearl/support-matrix