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The keyboard customisations are stored in the <calibre config>\shortcuts\viewer.plist file. Where <calibre config> is the folder opened when you press the library manager Preferences->Miscellaneous->Open calibre configuration directory button.
I suspect that file is not being created/updated for some reason. Could be your antivirus settings, or Windows Protected Folders settings. Exclude the <calibre config> from both.
BR
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