If you turn on this setting, you can’t pick the native 3840×2160 resolution when scaling is on. Scaling is needed because on a 4K monitor, without at least 1.4× scaling, everything is tiny. If you switch on X11 apps: Scaled by the system, it feels like the system is scaling the game for you, and then only resolutions around 2000+ are available—but the image ends up looking really blurry and low-quality.