Also clear:

Check the Windows Event Viewer (Windows) or system logs (macOS) for errors related to ArcGIS Pro.

Third-party Add-Ins (e.g., Data Reviewer, custom toolbars) sometimes intercept the save event. Go to and disable non-essential ones for a week to test stability.

Real-time antivirus scanning of .aprx files is a known deadlock cause. Add these folder exclusions: