There must be some reason for all the .25 stories about inadequate penetration. The only thing I can figure out is that people were using older guns with corroded/shot out barrels, or they are lying. My personal observations over many years are that the .25 auto, fired from a gun in good repair, has excellent penetration.
Many (possibly all) handgun calibers have been known to fail to penetrate a skull. These failures are the exception, rather than the norm.
The fact is that macho guys, "experts," instructors, cops, etc. have been telling people that .22s and .25s (and .32s) just don't work. The problem is that these calibers have been working for over 100 years anyway. While they aren't the best things for defense, they are still some of the smallest guns made. To this day, no one has made a .32 or .380 as small as a Browning .25 or a Bernardelli .25/.22. It's impossible to do so.
Most handgun calibers are not "instant one-shot stoppers," so the ultra small guns are still viable. Nothing short of a central nervous system shot can instantly incapacitate consistently.