I have reported this over in the bug reporting area, but I did some experimentation last night and came across an issue. My post is here:
https://forum.cockos.com/showthread.php?p=2004818
I also include several other posts where people report similar problems.
To recap, Reaper occasionally loses plugins and fails to load others. Sometimes a PC restart helps, others not. My thread above goes in to greater detail.
However last night, I downloaded a copy of the last release of 4 and installed as a fresh portable. I have 1 main VST folder with 2 supplemental folders where Waves and a few other oddballs sit.
I ONLY added my main folder and scanned. The plugins that were missing were suddenly there (plugins like SOME of the Neutron Advanced plugins (not all), Magnetite, some Sonimus stuff). They were back. This was good.
So I decided to add one of the other folders in order to get my Waves plugins back. I did that and rescanned. My Waves plugins came up but then the plugins that had been missing WENT MISSING AGAIN.
I added the third folder and ALL of my plugins went missing.
That told me there's an issue with the way and order that Reaper is reading these plugin folders. So I tried every combination of order in the VST directory until I hit one where all my plugins were there correctly. Just trial and error juggling the 3 around.
There are NO duplicate plugins across these 3 folders. There are NO 32bit plugins or anything like that. Something is wrong with the way Reaper is scanning things.
I got lucky here and set the house of cards up in the right order and things are okay now. I ported the folder order over to my latest version of 5 and things are good for now.
I know there are other users out there who have similar problems, but they've only got ONE VST folder so my trick will not necessarily work for them. I am convinced those issues are the same as mine, just manifesting themselves differently across users.