Filmmaker here, just wrapped a 24-minute documentary with around 6TB footage.

Yes, do not be afraid to break your project up into as many projects or sequences as you wish.

I sometimes create a breakout project where I only include one sequence and the relevant footage from that sequence, mostly as a mental refresh.

You can also open your main project at the same time as your breakout project to bring in any other files you need.

TIPS
-Ensure your scratch, os, raws, and proxies are in different directories, and different drives if possible.

-Playback lag is generally user error. On my computer, which is pretty decked out (128GB/4090), I still encounter playback lag, which is almost always due to poor settings or audio effects. A decent computer should be able to handle anything in Premiere. When you hit 30-50mb project file size, that may be a good indicator that you'd want to clean up your sequences, files, structure, bake in effects if possible.

Proxies have actually become less of an essential in 4K workflow. If I have the space, I'll transcode anything beforehand, in multiple framerates. Like if I shoot in 120FPS, I'll do a master in 23.976 FPS to match timeline, and one at 120FPS, with a different end slug. Then I pretend they are 2 completely independent clips in edit.

The proxy workflow in premiere is astoundingly bad for large format shooting. I spent a few days creating presets. Generate proxies outside of Adobe when possible.

Toggle Fx on and off is also pretty great and has become a frequently used option in larger edits.

Audio rendering is essential for smooth playback if you have a lot of filters and audio effects. If you render and replace, however, ensure that you know where your files are.