Hello:
Ah! Thanks, that screenshot helped a lot. You’re on the PDF tab. Click back to the Reference tab and you should now have a Save option.
It all depends on what the active window is. If you have the PDF itself active the Save won’t be clickable unless you make a change to the PDF – a sticky note or a highlight, etc.
If what you want to save is a change you made to the Reference, like attaching something or changing a field, the Reference tab itself has to be the active one.