If you are running 'Portable' (starting using the standard BAT), it expects TO USE specific differences in location of the configuration (and all the User-Security rights).
Running as a hybrid (Portable installed ON a internal Drive) requires you to modify the startup to fit your situation.
Most PI stick close to the Calibre model and work well when installed by the same Program as they are expected to run under
( <Configuration folder>/plugins ) . Some PI add another depth to their configuration for additional support to keep all the requirements together and not allow them to spread over the system.