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Unless you're building an app relying on office/COM apis

Or a proper development experience for Windows Forms and WPF.

What's different about the development experience. In Visual Studio it doesn't make much of a difference if you're target framework or .Net 5+.

Designer is still buggy, the new out of process model makes it incompatible with existing component libraries, requiring a rewrite.

In many things, .NET Core/.NET 5+ is the Python 3 of .NET ecosystem.