I use a 11’ GRX Di2 setup on my bike for 2 years now and so far it was working quite well. Although the rearshifting was no miracle, it was acceptable. I tried to finetune it testing between +1 and +5 adjustments, but I was always ending up with +3, that seemed to be the best one for it.
Las week, suddenly, when going on the easiest gear (biggest chainring of the cassette), the chain got suddenly dropped off the cassette (never happened before). I put it on the cassette again, but since now on it started to shift a lot between the nearby gears - like if the derailleur moved significantly toward the wheel. I stopped and readjusted - apparently, it started to work correctly only when I adjusted the settings to +9 (?!).
And although it seems to shift correctly now, there is one new issue I never faced before - shifting up is delayed. Not always, but often: 1-2s. This is extremely frustrating when climbing. It is like if the system was “thinking” for 2s, then it shifts without a problem. Trying to shift more than 1 step does not help, I still wait for those 2s and then it shifts 2 or 3 chainrings up.
Any idea what could have happened and how to fix it? I don’t recall hitting anything, there are also no signs of a hit on the derailleur. The batterys is fully charged.
No idea what to do…
I’d take it into a shop that knows how to work on Di2. 
Yes, there could be indexing issues that need adjusting, but there could also be wiring issues, or physical things that are causing poor shifting.
There’s really no way to know without taking a closer look.
Any chance the derailleur hanger is bent?
Hanger. And have you removed your rear wheel? Is the Thru axle fully tight?
Probably not the culprit but the clutch sometimes causes issues in the easier gears and after two years could probably use service.
I was also going to suggest bent hanger
Did you change out your chain recently?
If so be sure that it’s not rubbing on the little tab in between the 2 jockey wheels. Mis threading can cause your issue.
Find the correct guide here and redo the set up from scratch. https://bettershifting.com/
Thank you for all the hints. Let me address some doubts:
- Indeed I was removing the rear wheel recently. Anyhow, the thru axle is fully tight and the bike made some 300km after the wheel replacement without any problems.
- Hanger. It seems perfectly ok. I used to have a spare one somewhere just in case, I could try replacing them if I find it. Anyhow, no signs of hitting it, and the issue appeared suddenly. It shouldn’t get bent just like that, without being hit, right?
- The chain is not yet too much worn. It doesn’t seem to rub anything, threading is ok.
- The shop that knows how to work with Di2. I haven’t identified one so far anywhere close to me. Might be the only case if I don’t solve the issue myself, though…
You won’t see signs in the hanger. It might be just a fraction off, sufficient to cause you many headaches. I strongly advise you to check it before proceeding with anything. A top-tier brand new goupset will fail if the hanger is bent unless we are talking about the new Sram, which isn’t the case.
I bought a fatbike last year, and it came with Deore XT. I had a hard time fine-tuning the gears. I brought it back to the store and asked to check the hanger, and they denied saying that the cable was flat. Then, I replaced the cable and tried a million times to fine-tune it to no avail.
I then bought a tool to check the hanger. It took me 10 min to figure out that the hanger was bent, and 5 min to adjust the derailleur. It was like magic, spot on in 15 min.
Worst-case scenario, you’ll know for sure that the hanger is aligned, and a very important tool in your box.
Thanks for this link AlexMartins. Do you also have a link to kinda manual on how to use it? I mean, a verified good manual/movie, not to go through 1k crappy ones before finding a good one 
Sure I do ParkTool video
If you have a QR rear wheel hanging about here’s the tool-less way to align a RD hanger.
Straighten/Align Bent Derailleur Hanger Without Special Tool (youtube.com)
I asuggest you heed @angusr’s suggestion and follow the Di2 adjustment instructions at bettershifing.com.
It’s not the number of clicks in/out that matter but whatever it takes to align the chain on the middle cog.
Also check whether chain clearance on the largest cog is to spec using the B screw.
I just checked the hanger. It had 5mm of horizontal bent, and 13mm (!) of vertical bent 
I corrected it and consecutively reduced the microadjustment from +9 to +4. I also had to move the derailleur significantly away from the cassette (which is strange - just wonder if I could mount the derailleur incorrectly. GRX is a bit different than my previous derailleurs, it has a microarm between the derailleur itself and the main mounting screw).
The shifting seems anyhow ok now, although I still need to check it during riding.
Thanks a lot - I have never ever been checking hangers before and somehow never had an issue with it before, neither (or at least, not big enough to realize the reason).
Anyhow - I was a bit surprised with the force (very little) needed to adjust it. On one hand it is a big lever (the tool used to adjust), on the other, now I feel like anything can bend this hanger any time… 
Surprised you couldn’t see that from 30 ft away
#metoo 
But this hanger is very small, maybe that is why. Easier to notice on a longer one.
If you get to the point of considering changing it for a new one, maybe take a look at the ones made by Pilo. Decent quality CNC machined pieces.
Its website is https://pilo.co.il but there may be a dealer in your own country too (here in the UK for instance it is https://gearmechhanger.com )
I was like you, never checked it until I really needed. Then I realized how important this small piece is.
It’s hard to determine if the hanger is bent by looking at it in “regular” cases.
I’m glad you have a starting point to figure this out.
I’d recommend getting a backup hanger on hand. Alloy hangers don’t last forever, and bending them back and forth will soften them really quickly.
As you can see, they aren’t actually super tough (that’s sort of the point)!
I’m glad you were able to get this sorted out! Throwing a tool on your hanger is easy enough and when your shifting suddenly doesn’t work as it should (especially with Di2), and it’s likely that your hanger is off. It doesn’t take much to bend them so watch that drive side of your bike!
I was looking at the Silca hangers recently after getting an email on them. Is that an omen?
I do have a spare for my MTB and fat bike because they are the bikes that would likely end up needing a replacement after a huge biff on a rock or stump. I’d be devastated if I ended up needing a replacement for my Roubaix so have been thinking of getting a spare from them. They look pretty cool, and are somewhat lighter and stronger (supposedly). I should probably throw the DAG on each bike at the end of the season and see if they are still straight and true. I don’t have a bike with the UDH yet, at least I don’t think I do. But is the UDH (Universal Derailleur Hanger) really universal? Forgive me for my jaundiced view of standards in the bicycle industry…
Glad you found the problem! And eyeballing a hanger is not exactly easy. I had a bike at a recycle a bike that I was SURE had a bent hanger, and it was actually, surprisingly, straight. 
