1. Yes when you start the game, there are some choices that are permanent. Even if you reload a save, the choice will be automatically inputed and you can't undo it no matter how far you go back. This is because of the persistent file in your saves. It records your current progress and every choice you choose.
2. If you want to restart/redo the game you have to (grabbed this advice from the discord):
Press "Win + R" on your keyboard to open the Run window.
Type "%APPDATA%\RenPy" into the box and press Enter.
Find the folder named "emptybox" and delete the entire folder.
Reinstall the game, and you should be able to start fresh!
This will delete your existing save data, so make sure you're okay with losing your current progress before doing this!
3. Yes you can be locked out of the game at some point in your playthrough if you choose a certain choice. If you'd like a loose guide, there is a guide in the Empty Box discord if you think that will help!
4. When you get to the true ending, there's not a method of collecting all cg's and endings, because once you select the LI that you want the game only gives you the cgs of that LI when you beat the game. I've seen people make multiple windows accounts to get all the the cgs, but it's not possible to collect all of them on a single windows account.
Hope this helps!