As you can see in the attached GIF, when you open the menu to configure you pop-up, there is a delay in loading the menu item for "Filter Edits".
This causes the "Remove Pop-up" button to be moved to where you've moved your mouse to "Configure Pop-up", causing you to click the "Remove Pop-up" button instead of what you wanted to do.
This doesn't just remove the popup, but it completely erases what you had in there before. The only solution is to refresh the map without saving so either way you lose unsaved work or have to redo work.
In lieu of you having to do some programming to fix the delayed load, perhaps you could just rearrange the menu. I recommend just moving that "Filter Edits" item to the bottom to avoid misfires.