This control is always disabled when you open the Global Hotkeys tab-page. Only after having selected a Shortcut-Location item in the Shortcuts Dropdown List this control becomes enabled:
If the Shortcut Location selected in the Dropdown List contains a PA-RUN Shortcut Link then this checkbox is checked:
If the Shortcut Location selected in the Dropdown List does NOT contain a PA-RUN Shortcut Link then this checkbox is unchecked.
If you click on this checkbox then the Shortcut-Location Save-Button becomes enabled: 
See also: PA-RUN ShellLink Shortcuts