My system: Debian Jessie and PoL 4.2.10
As I understand, the error I'm presenting is not game related but PoL related, please bare with me the explanation of the whole issue if you're happy to do so.
League suffers (I believe) memory leaks, thus the FPS dramatically drop as the games last longer. In my case from about 120fps to 15fps at ~ min 30. This is using the standard 1.9.2-LeagueOfLegends5 wine. This issue is from the client, not the loader, and I have tried this before the new client came up already, but it has gotten worse lately.
I read in some reddit post that using a staging version, and enabling CSMT could solve the issue for some people, so I wanted to try. The PoL configuration window allowed me to download and install all wine versions (including said staging versions), but they could never run. This particular example is the debug I get from 1.9.2-staging-LOL3, but other versions would give the same error:
[07/12/17 00:55:27] - Running wine-1.9.2-staging-LOL3 LeagueClient.exe (Working directory : $MY_HOME/.PlayOnLinux/wineprefix/LeagueOfLegends/drive_c/Riot Games/League of Legends)
wine: failed to initialize: //lib/wine/ntdll.dll.so: cannot open shared object file: No such file or directory
I cannot even go to the configuration of the installed wine, or install libraries for that matter, it also bugs there.
The installation folder for the new wine versions, does include the library, I.e:
$MY_HOME/.PlayOnLinux/wine/linux-x86/1.9.2-staging-LOL3/lib/wine/ntdll.dll.so
Installing a newer PoL version did not help, so I've reverted to the PoL I can find in pip (4.2.10). Reinstalling wine gave me no results either.
TLDR: I can only use the wine version that my game comes with. Other wine versions do not run and complain about missing ntdll.dll.so (which apparently is in the right place).