It's crazy how long this issue has existed and keeps resurfacing! There are countless threads online (mostly outdated by new code releases) discussing it. Many of them have a kernel of truth, but most of them miss an essential point. However, let's be very clear about a few environmental concepts first. 1) You must go to Silverlock.org to download SKSE - the executable is not on NexusMods. 2) You should install the AE version build 2.1.5 if you have SE (not the SE v2.0.20). 3) Use your mod manager (Vortex, MO2 - not NMM!) to install it. New versions of these now do it correctly and there's no need to install it manually like the old days.4) All of the articles telling you to edit the mod manager .ini file and add a "*" in front of SKSE entry are based on old versions that didn't work well. This is obsolete in 2022. The second major issue that people thrash over is where they've installed their games and mods. It's perfectly fine to install Steam itself in the default location of C:\Programs. However, this is less than ideal for your games and mods. Windows security is very picky about security privileges in systems directories. Script injection engines like SKSE (and mods that depend on them) do a couple of things that require admin privileges. 1) If your normal Windows login has admin privileges (very poor cybersecurity practice), then you're home free and everything will run fine if installed in C:\Program (or anywhere else). 2) If you're logging into your PC with a non-administrator account AND you installed your games in C:\Programs, you're going to need to follow the admonitions of the various threads and use the properties tab of the SKSE_loader.exe to "Run this program as an administrator". 3) You really should install Skyrim, SKSE and everything other game on a separate drive or partition. This enables all of the executables to function normally without needing elevated privileges and keeps you less vulnerable to rogue mods and other threats. Great you say, I've installed SKSE correctly from Silverlock and I've also installed it in the correct location with the correct privileges on my PC. However, when I launch Skyrim via SKSE (not SkyrimSE.exe), I still get this stupid error message! Have you stopped to really observe what's happening? SKSE is clearly launching and so is Skyrim. Thus, the problem is with SkyUI - NOT with SKSE! For some reason, it's not correctly detecting that SKSE is already running. Well, WTF? Without getting into the weeds, SKSE opens a connection to Steam to authenticate you so that it can launch Skyrim. Effectively, it's like when you're in Skyrim and you open the door without knocking - inhabitants may be surprised or angry. The door is open, but you're not really welcome. On the other hand if you knock, they open the door and you have a chat and they invite you in. That's what happens when you launch the Steam client first and THEN launch SKSE. You can even close the Steam client after it completely launchs and SKSE will still launch Skyrim without any SkyUI error. SkyUI is like your follower who stands outside the door of that private residence and says "that's not right of you going in there without permission." It sees the open door, but refuses to participate in your plans. So what are your options? 1) Manually launch Steam.exe, then launch SKSE64_loader.exe 2) Add SKSE to your Steam library as an "external application" and launch from there3) Add Steam and SKSE to Vortex and launch them in that order (waiting for the Steam client to appear before launching SKSE)4) Write a cool batch file to automate this for yourself or download a SKSE launch mod