And it happened again today:

I’ve solved this problem before but had forgotten what I had done to deal with “The iTunes Library file cannot be saved. An unknown error occurred (-54).”

A quick search around yielded a range of voodoo solutions but the one that did it the simplest; I asked Disk Utility to repair permission. This is the comment that solved it for me:

 https://discussions.apple.com/message/17805319#17805319
“From an OS9 reference, error -54 is a software lock on a file or a permissions error. (Some of the old codes still apply to OSX although there is no formal list of OSX error codes.)”

I’ll buy that. You can find the Disk Utility here:

/Applications/Utilities/Disk Utility
1. Choose your disk in the list on the left.
2. Click “Repair Disk Permissions”
3. Come back later and they’re fixed.
4. Restart iTunes.