You receive the following message in Microsoft Defender for Endpoint on your Mac:

Real-time protection could not be turned on. Contact your administrator.

Apple requires that all new system extensions being installed from third-party developers in macOS be manually allowed.

1) Open System Preferences.

2) Click Security & Privacy.

3) In the bottom left-hand corner, click the lock icon.

4) Authenticate using Touch ID or the username and password of an administrator on your Mac.

5) In the left-hand pane, ensure that Full Disk Access is chosen. Then, check the boxes next to the following:

• Microsoft Defender ATP.app
• Microsoft Defender ATP Endpoint Security Extension

6) Close System Preferences.

Outcome

Microsoft Defender for Endpoint will function as expected on your Mac.