Last few years I ran a GRX 11s Di2 setup with 46/36x 1140 with an old XTR cassette and Wolftooth Road link. That worked beautifully so I tried to do something similar with the new 12s GRX Di2 2x.
Recipe:
Switch to 46/31 rings from the standard 48/31 or 46/30. The smaller 15t step makes it possible for the RD to have enough take up.. just.
Wolftooth Roadlink DM
10/45 Shimano cassette
microspline freehub body
Cut chain so its as short as it can be and still cross chain bigbig with a bit of slack on the RD.
Cross chain bigbig is a tad noisy due mainly to the wider chainline of GRX. I wish there was a way to get 44/30 12s compatible chainrings with a standard road chainline. That would be perfect.
With my tires, I have a 19.4" low, 130" high and 668% range. Insane gearing!