Found in Unity 2021.2.17f1
For the last year or so we’ve been using PlayerPrefs to store save data, and would routinely delete the entire folder via RegEdit to flatten the save and start over. This never caused a problem.
However, with the target platform set to Android (and/or having upgraded to 2021 from 2020), deleting the root key renders PlayerPrefs non-functional when running in the editor until Unity is restarted. Any attempt to write a value produces a generic ‘PlayerPrefs could not write value’ error.