Explaining "Apply Once and never apply again" in plain English

"Apply once and do not reapply" means that the setting will be applied the first time the GPO is run against the target user or computer object, and isn't applied again on subsequent runs. It won't be re-applied on GPUpdate.

Think of this as setting a "get started" setting that the user can then change, for example setting a preference for the default homepage in IE to be www.example.com the first time a user logs in and generates their profile, but allowing the user to change the homepage themselves afterwards.