Regarding differentiating python via CPython, theoretically yes, though practically it is likely more wise to use something like Numba which takes Python to LLVM directly to avoid a bunch of abstraction overhead that would otherwise have to be differentiated through. Also fun fact JaX can be told to simply emit LLVM and we've used that as an input for tests :)

You can explicitly define custom gradients by attaching metadata to the function you want to have the custom gradient (and Enzyme will use that even if it could differentiate the original function).

Integral types: mayyybe, depending what exactly you mean. I can imagine using custom gradient definitions to try specifying how an integral type can be used in a differentiable way (say representing a fixed point). We don't support differentiating integral types by approximating them as continuous values if that's what you're asking. There's no reason why we couldn't add this (besides perhaps bit tricks being annoying to differentiate), but haven't come across a use case.