I'm also not able to synchronize files with the V4 uploader, from local HDD to pogoplug. Used to do this with the web interface and "backup", but this is no longer possible since I cannot set my PC as source.
I have created a ticket and received a swift reply.

The suggestion was to add exceptions to firewall and antivirus software for pogoplug exe files. Also tried opening relevant ports on my router. It didn't work for me, but perhaps it will work for some of you guys.
Also tried to re install the uploader which didn't help.

But if the CE eng. are aware of this problem then hopefully a solution might be on the way? So far I'm no longer able to create automatic backups of my files to my Seagate Goflex net pogoplug. :-(

Well it is March 7th and I do not see an answer posted. I have the same issue

I have the exact same problem with my documents and have an open ticket with support. Shared My Documents folder with them and they say it syncs fine. She is going to talk to support. The last time I had a problem they could not figure out they went to support and never came back. They finally said try the new version of the software. at least 2 months after the ticket was opened. SO I don't have high hopes.... Oh yes this is happening on 2 different machines. One is XP and the other windows 7. They use different AV and firewalls. I like you don't believe it is a port issue since all other files back up fine on both machines. So I'm not holding my breadth for an answer.

If you're running Windows, I suggest you use Microsoft's RichCopy to handle the backup/synch process. It's very robust and has good optionality. And it's free.