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While towing a generic heavy 5th wheel, the rear of the truck will probably sit 2-3 inches lower than it rides empty. I assume that a truck maker takes this into account when designing the driveline, so that even while the rear end is squatting the driveline angle is correct. I am considering putting a Kelderman or similar 4-link with airbags. These bags are adjustable. Is there a good reason not to run the truck, in general, with the rear end sitting lower than stock? The 2019 F350 4x4 that I own sits very high in the rear.
Short answer: Yes, the manufacturer takes all of this into account.
The aftermarket suspension folks usually do as well. Usually.
I don't think any of them take into account the results of mixing or combining various systems. Well, they probably have at one point or another, and subsequently discovered that they don't want to outwardly appear to start to consider taking into account the results of mixing or combining various systems.
Years ago, my new 1991 F250 460 gas, would shudder very badly accelerating from a stop with the 5th wheel attached. Visits to the dealer yielded no help. I then reached out to Ford Customer Service who put the dealer into contact with a local retired Ford suspension engineer. He met me at the dealership with me pulling the 5th wheel. After a short drive around the block, he crawled under the truck with a protractor and took some measurements. I then unhooked and he did the same. With those measurements he went back home and within a couple weeks had found the p/n for a center bearing support that was a size that would mitigate the angle change with the 5th wheel hooked up. After the new support was installed there was no more shudder when taking off from a stop.
So if you do experience some drive line issues, they can be fixed with assistance from knowledgeable people.
That driveline shutter has plagued some trucks w/ center support driveline carrier bearing on all the Super duties. Ford makes a spacer kit for the bearing to lower off the frame to correct the angle. Usually 3/8" spacer shim is enough.
On edit I'll try to add the Motorcraft part# and there is aftermarket companies that offer the spacer too.