Why does Android Studio get into this failed state (builds but displays App(x) & doesn't want to run)?

Question

Notice that little red x on the app button? It means I cannot run, even though it builds.

Running version 4.2.1 of Android Studio:

Then, if I try to run, I see the following:

Clicking the [Fix] button displays the following:

Answer 1

As I was writing up the question, I stumbled upon the answer.

The answer is that my build variant was set to Release:

I changed it to Debug and that fixed it.

That's interesting though, because I can build the release version and I do have a signing cert but it couldn't find it this time. Very confusing.