You can set how the helpdesk handles Agent replies to an Email notification.

Any content an Agent adds above the REPLY ABOVE line can be treated either as an Agent note or sent as a reply to the User.

To change this, in Channel > Email > Settings, check/uncheck the Process email replies as notes instead of Ticket replies option.

All notification Emails make it clear to the Agent what will happen if they reply by Email. If you change this setting, it will only change the behavior for notifications sent from that point on: you will never have a situation where a reply is actually handled differently from what it says in the notification text.

Agents can override the default behavior using the #note and #reply  Action Codes.