I've got an 8gb wd usb external plugged into my pi4 (libreelec) and it works fine.

However I also created the partitions and formatted it from the raspi4 using buster and gparted.

No experience w Mac's

There’s no reason why 4tb won’t work, only that by default retropie installs into folders in the home directory of your user account ... so either you ensure there’s enough space partitioned there, OR you move the directory to a path with more available space and create a link in your home directory to that path.

So I played around a bit, got a new SD card with the image on it.. did all the typical tweaks (enable wifi, disable overscan). I then followed the guide up to editing the fstab. Plugged in the UUID appropriate for my drive, and used this command:

UUID=******** /home/pi/RetroPie ntfs rw,exec,uid=pi,gid=pi,umask=022 0 2

Essentially, I'm using the vfat example in the guide, and just changed it to ntfs. The rest of the options I'm not sure what are for, but it looks like user permissions (like read/write/execute/etc) for the path and it's specifying the user as pi so I left that in there from the example. I'm not sure about the umask bit, so I just left it too. If somebody can clarify on what all those are, I'll edit my setting if needed. But for the most part, it looks like it's working. I was SFTP'd into the Pi prior to rebooting. I could access /home/pi and everything else on the system just fine, but not /home/pi/retropie. However, after rebooting, that last /retropie/ bit opened up and gave me access to things like the bios and roms subfolders. So I'm assuming that means the automount DID work. The only way I'll know for sure is if I transfer in bunch of files over 8gb, because that's the limit of my SD card. :)