I haven't experienced the 'npc voice bug' some others are reporting, I think that may have been fixed with the latest Proton versions. As for modding, I experienced 3 issues unique to Linux/Proton;

1. Not sure how STL & Vortex work together, exactly, but I'm not sure if launching SKSE through Vortex uses the proper Proton version, or at least the multiple gigabyte shader cache. The mods worked, but the framerate was extremely unstable and quite slow. I fixed this by renaming skse64_loader.exe to SkyrimSELauncher.exe, making a backup of the old launcher just in case, and running the game directly through Steam. It ran with similar performance to Windows, however there was a new problem...

2. The game only loaded certain mods, and upon trying to load a save gave me a warning that the vast majority were missing from my system. So, in Vortex's settings, I changed the deployment method from 'hardlink' to 'move', which, unfortunately, didn't do anything. I then went into Bethesda's native 'mods' menu, and saw that the mods were indeed all there, but none of them were enabled... Enabling them and sorting the mod order with this GUI was painful, a recent report suggested modifying ~/.local/share/Steam/steamapps/compatdata/489830/pfx/drive_c/users/steamuser/AppData/Local/Skyrim Special Edition/Plugins.txt which is probably much more ideal.

3. The final issue. Some mods cause stability issues w/ Proton that aren't seen on Windows... A bit into my playthrough I started experiencing crashes after less than a minute of play, often when looking at containers. Out of curiosity, frustration, and the desire not to always be booting into my Windows drive, I tried disabling one of my mods that would activate whenever looking at containers; 'QuickLootRE'. This fixed my issue and now the game plays perfectly!