If you upgraded your PC to Windows 10 since you last uploaded to the scanner - it won't work.
I don't know if this applies to you:
Q: I downloaded Windows 10, and now my scanner does not work.
A: All of our scanners with native USB just plug and play with Windows 10. For older models (i.e. “XT” or “X” models) that have a serial connection, older USB-1 cables will not work, as Prolific changed their drivers several years ago to only work with their newer chipset that has anti-counterfeit features. At that time, we changed the chipset in our USB-1 cables. So, if you have an older USB-1 cable it won’t work with Windows 10 (or really w/8 using current drivers). Newer (last couple of years) cables will work.
You might try doing the Auto Detect (Start Auto) in the Read window. (Its always good to do a read as a very first step, just to be sure you got a good connection, then make the programming changes).
It could be an issue of wrong com port choice or baud rate, if the cable is appropriate.