Get-Recipient -Identity email@example.com
This will return the recipient object for whoever has the given email address (including aliases). Since emails are guaranteed to be unique this should never return more than one record (I believe).
Get-Recipient -ANR user
You can use
-ANR to search using Ambiguous Name Resolution (so you can type their first, last, username, etc), but while ANR will match a user's primary email address, it will not match their other SMTP aliases. ANR can return multiple matches (so ensure your code handles this case).
Get-Mailbox is not sufficient to confirm that an email address is unique, as it will not necessarily return contacts, or records from external or legacy systems. It returns mailboxes... and while all mailboxes have an email address, not all email addresses are a mailbox.