Highrez

XMBC Version: 2.20.5
Installed or Portable version: Installed
Windows Version: Windows 10 22H2
Mouse Information (brand/model): Kensington Expert Wireless Trackball
Relevant Computer Information (CPU, RAM etc): N/A
Did the problem occur after an upgrade of XMBC? (If so, from what version?): No
Did the problem occur after a Windows update/upgrade? (If so, from what version?): No
How long have you used XMBC?: 5+ years
What language and keyboard layout do you use in Windows?: English QWERTY

Clear description of the problem - try and include as much information as possible, including what button and mappings you are having problems with (if applicable).:

I can't upload pictures, so here's my setup from XMBC:
Left: Chording With Right: Back
Right: Chording With Left: Refresh
Middle: Middle
Button 4: Back
Button 5: Forward

I've experienced this issue with a few different games from Steam as well as some websites, but I always forgot to write it down to open a thread about. When XMBC is enabled and running my default profile, my computer won't register a normal click. To get it to register, I have to click and hold, then release just after the chording "+" disappears from next to my cursor.
If I disable XMBC from the taskbar icon, or if I switch to an empty layer, clicking goes back to normal

To see it in action, you can visit a public instance of a photo manager called Photoprism. The URL to the demo site is demo.photoprism.app
When you hover over a thumbnail, a small circle outline appears on the bottom right of it. When you press it, it should fill in the circle to indicate it chosen for a multi-selection
If it would help to have more applications that show this, I can go through my Steam games and try to figure out which ones do it.

I'll have to look into this. The problem with chording is that it has to block the physical button until it knows if you intend to chord or not (so until it times out - the grey cross goes away) or you press a chorded button (the grey cross turns red). Once it times out, it simulates a button down of the chording button. But some applications block simulated buttons - in which case your in trouble - this may be the case with these apps - and if that is the case, there may be nothing that can be done, other than not using the button for chording.

For that reason, I never recommend using chording on the left button - because there are some limitations, particularly that one with applications that don't like/block simulated input! The only immediate solution I can think of is to create a profile for those failing apps, where chording is disabled on the left button. Not ideal but there may be no other way if the app itself is blocking simulated input (a bit surprised that a generic photo app would do that - its usually games that block simulated input, to prevent cheating etc!)