It's /boot is on SD card and rest of it is on M.2 via USB3 (just be aware that Rpi 4 has its own software performance kinks and does not have VP9 or AV1 hardware decoding but if can you live with those). However I have successfully run Linux from SD card using x86 laptop in work setting about 0.5 year (and it is now inside my phone and still OK). Sometimes apt got stuck and I had to reboot.
SD Cards's are not very expensive and you can make backup images.
But corruption might happen and I have definitely seen it happen in few pen drives around 700 bulk. Depends on luck and quality, I guess.
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Ok, we are off-topic and that discussion deserves an own thread...
The development of proper software that unlocks all features of the Raspberry Pi is delayed. So there are some features planned by still not realized to date.
Booting and runnung the OS from an USB storage device is such a feature.
The Pi 4 features a faster SD card interface which doubles the data transfer rate compared to the previous models.
But you'll need a higher speed class of SD card (UHS-I Class 3) to benefit form that.
Another point is the GPU and the supported video codecs. No devices up to date supports AV1 decoding implemented in hardware.
I guess we'll have the wait for Pi 5 for that feature.
I've read an article in the German magazin for computer science and the experts claim that the Pi4 has a build in hardware video decoder for VP9, but it's not usable right now because software support for it is missing right now.
According to the said experts, the Pi4 is capable of both hardware accelerated encoding and decoding of H.264 and H.265, as well as JPEG,
and VP9 decoding only.