A couple of years ago I wrote about the ".22LR as a defensive round". I argued that the lowly .22 was underrated for self-defense purposes, and that with good ammunition and proper shot placement, it could still serve that purpose. I recommended CCI Velocitor as my primary choice of ammunition for that application.
Now, courtesy of Wirecutter, we find this video, illustrating what happens when that round is shot into a chuck roast at 300 yards' range. The results are impressive, and (I think) bear out my earlier recommendations. See for yourself. (I recommend watching in full-screen mode for best results.)
Admittedly, those shots were fired from a rifle, not a handgun: but their reduced velocity at long range was less than the same bullet would attain if fired from a handgun at defensive distances. That's outstanding performance for such a small round.