The biggest issue is it makes applying any sort of transform onto the bones a bit more difficult, as the positions are mirrored but can be mirrored on only one axis if there is a non fully negative scale (like (-1, 1) for example). I remember when I was doing some OpenGL stuff that matrix math for negatives had some quirks with skinning for animated characters, but it’s been a long time since I’ve done OpenGL work directly and admittedly I never got too far into OpenGL 😅

Thankfully any complexities like that are generally handled by the game engine anyway. The only time I’ve had a bunch of issues with it in modern game engines is directly modifying negatively scaled children transforms (like bones) and doing calculations with non-negative stuff. I’ve also had some physics quirks in 2D a couple times with negative scales but I think that was more due to the non-fully negative aspect (flipping stuff by changing the sign on the X axis) rather than it just being negative.

Edit: I should add that if you are not having issues currently with any negatively scaled stuff, then you’re probably good to go. If there are issues, I’ve found they surface pretty quickly generally.