Shimano M8100 derailleur compatibility with SRAM XPLR cassette
 

I really like the ratios of the new XPLR cassette from SRAM, but I'd like to have a mechanical drivetrain. This setup is going on a gravel bike FWIW.

Wolftooth had the best images that I could find about the design differences in the chains. It looks like the main difference between the Shimano Hyperglide chains and the SRAM Flattop chains are Shimano's extended link plates that require chamfers on the cassette/chainring. In my head, that means that the M8100 derailleur should work fine because having the chamfers to accommodate a Hyperglide chain should not cause a Flattop chain to bind.

Does anyone have any feedback on whether the combo below would work? I suppose my main concern is cassette spacing differences between XPLR and M8100.

Derailleur: Shimano RD-8100-GS (12S, 45T low sprocket max)
Shifters: Microshift Shimano MTB 1X12 (Actually a Gevenalle lever)
Cassette: SRAM XPLR XG-1271 (10T-44T)
Chainring: Garbaruk Easton Cinch Round (42T, 12 speed for SRAM AXS Flattop)
Chain: SRAM Force CN-FRC-D1 (12 speed Flattop)

PS: If this won't work, I'll just run the 10-45 Shimano M8100 cassette, but I really don't need that tight of gearing on the bottom end of the cassette.

You made the right choice to match the axs chain with the xplr cassette. I tried a shimano xt 12 speed chain with my force axs 10-36 and 10-33 cassettes. It didn't work terribly with the 10-33, but the wider chain had hesitant shifting in the 13-14-15 area that micro-adjust couldn't fix. My 10-36 setup uses a 33T RD and works fine with an axs chain, but poorly with the xt chain. FWIW, an axs chain works great with a Campy 12 cassette.

As long as the shifter works properly with the RD, you should be good.

Which RD are you using in that setup? I figure the flattop chain wouldn't cause any issues, but I'm not sure if the XT RD and shifter will talk nicely to the XPLR cassette.

My setup is force axs 2x with shimano grx crank, so my shifters, RD and cassette all match. Shimano 12 sprocket spacing might be a bit wider, but I've never read anything about it. Sram axs and Campy 12 sprocket spacing is very close to the same.