Replacing a 'missing' reference in prefab editor view will not flag the prefab as dirty, and as such, will not save unless you toggle other fields which do flag it as dirty. Quick test using 2 sprites: 1. Create an Image, assign a sprite and make it a prefab. 2. Delete sprite used above. 3. Open Prefab Image in Prefab Editor View. 4. Replace the 'missing' sprite reference with second sprite. 5. Note that Save does not become enabled. 6. Leave Prefab View and note the change did not happen. 7. Repeat 2-3 but this time flip some random field and verify save becomes enabled. 8. Save and back out, and note this time the missing reference update correctly saved. Doesn't have to be sprites/images, seems to be any "missing" reference that replicates the issue.