Design our SharePoint lists so we do not have more than 50,000 items with unique permissions

Hello johnjohn-Peter 

in libraries you can create documents in folders, the documents will be inherit the permissions from folder, in this case only one permission will be unique, but in lists.....

I see this two possibilities: 

1. Create a list and give users access to the list, they see the most items, this items will be inherit the permissions. Other items have unique permissions and other users have only access to this items, but not to the whole list and they don't see all items with inherited permissions, only the specific item level permissions.

2. Create more then one list

Good luck.

Best, Dave