I don't know the actual issue, but I found a solution that works for us. We noticed that our vports that were on the layer defpoints would be "untouchable" whenever layer 0 was turned off or frozen. As several others mentioned, we now have a dedicated vports layer set to not plot.
Unfortunately, this still happens to me too. After repeatedly trying different work-arounds I found this to be the easiest way to select my vport: 1] select the Pspace tab you need to be in 2] in 'Properties' palette click on 'Quick Select' at top right then in the 'Object type' drop-down select 'Viewport. "Value' field is ByLayer (see attached 'Quick Select' screen shot for settings). 3] Click OK and you should see the vport highlighted with grips.
Check your layers perhaps your veiw ports where on a frozen or off layer.
Make sure layer 0 is unfrozen and defpoints is unfrozen. Click into the model space tab, then back to paperspace. Then REGEN.
When working with lots of viewports on multiple layouts in AutoCAD, users can run into a problem when they create a viewport, and it
disables or turns off a previous viewport, making its contents disappear.
This is usually solved by setting the MAXACTVP system variable to a higher number. This sets the maximum number of active viewports allowed in AutoCAD. The maximum is 64.