It's somewhat difficult to say what the 'general' issue causing this is, but I was able to pinpoint one instance of the Ctrl+S 'Save' function not working in an open document.

Note that this seems to only apply to the Keyboard Shortcut, and the Hambuger Menu 'Save' function works as expected.

See attached video.

Repro Steps:

1) Create a Studio Project featuring a MainPage.xaml

2) Navigate to the Interactivity Panel, select the root Grid from the Navigator, and then add a 'DataEvent' Trigger to the Grid.
This will open the DataTrigger's Properties on the right of the application window.

3) Add an Action to the Trigger created in Step 2.
Observe how this has created a 'ChangePropertyAction' Action.

4) Press Ctrl+S to save the current document.
Observe how the document has successfully saved.

5) Change the Action created in Step 3) to instead be a 'ControlStoryboardAction' Action.

6) Press Ctrl+S to save the current document.
Observe how the document has not successfully saved.

7) Click on any selectable Element in the UI, then press Ctrl+S again.
Observe how now, the document has successfully saved.

Expected Results: The 'Ctrl+S' save action takes effect no matter what is selected, or actioned within the Studio UI.