To check whether it is the (shift) region that is broken...
Can you shift click on the normal region, while in combat, and have the shift click action occur?

I have a straight repeater region, which passes everything to my healer or healer group.
And use Grid + Grid Custom Layouts for the unit frames.
And Clique to interpret clicks.
I commonly use Alt + left, Alt + right, Ctrl + left and Ctrl + right, as my clicks to heal with.