It's not. I haven't come across any software that relied on it.

striking · on Feb 24, 2016

Somewhat infamously, GRUB failed on Intel Macs (in 2006?) because it tried to use the A20 gate, and Apple refused to emulate it. It's fixed now, though.

userbinator · on Feb 24, 2016

Very old (as in pre-386, or even pre-286) DOS software, written for the PC and only the PC, might depend on it. If I remember correctly, archive.org has a whole section devoted to ancient DOS software, so you might find something in there.