Keep the modified Layout.bin within reasonable file size limits compared to the original to avoid memory errors.
C:\Program Files (x86)\Steam\steamapps\common\Resident Evil 4\BIO4\ImagePack\ Layout.bin File For Resident Evil 4
The most famous use case. A randomizer mod shuffles items and enemies, but a room randomizer (which teleports you to a random room when you open a door) requires rewriting the connection table in Layout.bin to point to the wrong (or randomized) exit destinations. Keep the modified Layout