Which driver are you using? If ASIO, it may be that another program is latching on and not letting go of the L22. That happens here sometimes. I have Sonar/Preferences set to share but it does make a difference which program opens first. e.g. if I open Edge and play audio/video, I cannot then leave Edge open and open Sonar and get sound. However, if I open Sonar first, I can open Edge and play media (or at least record sound in Sonar). I have the L22 and also use Reaper & Vegas. It does happen with other software although Sonar may be a bit pickier - don't remember how the other programs react.
Not at the computer atm but I do remember some peculiarities especially using ASIO. More information on your circumstances would be helpful.