I've got an 05 F150 4x4 with a 5.4 that has developed a clicking tapping noise when towing our 21ft 4,700ish pound camper.

It comes on when going up a very slight grade at around 60mph.

At first I thought it was pre-ignition, but I have convinced myself that it is not.

The sound is similar to pre-ignition, but less harsh and a bit quieter if that makes sense. It is loud enough to hear at 60 with the radio at normal levels, but I'm sure if I had the radio loud enough, it might not be loud enough to hear.

I dont think it is preignition because I ran 2 tanks of premium thru the truck while towing and the behavior has not changed.

Also I connected my phone to the ECM with the Torque app (incredibly useful) and got no misfire codes. At one point I let it go on making the noise for 15-20 sec and go no check engine light or codes or anything. So I don't think it is engine related.

If I am driving along and come to a grade that is enough to cause the truck to downshift out of OD, or if I tow with OD locked out, it doesn't happen.

It is only on very very long very slight grades, and only when towing. I would estimate that it takes about 1.5 miles of constant throttle at just below the point where the truck would downshift.

Once the noise starts if I let off the gas slightly for even a second or two it will go away.

If it is clicking and I press the pedal further (even all the way down) the noise does not change or get louder or faster with RPMs.

At this point I am thinking that it may be the Vacuum hub disconnect system, but everything I have heard on videos about diagnosing them it sounds more like a groan rather than a click.
click.
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This is definitely a click noise not a groan or whine.

And again, I've never heard it while not towing

 

the front hubs are vacuum controlled.. takes good vacuum to keep the OFF and in 2 x 4... when you loose some vacuum, they engage or start to drag and try to get into 4 x 4... That is the best guess since it only happens when you accelerate or push on the throttle as that is when your vacuum DROPS.

 

As far as the sound itself, if it sounds like a spinning ratchet wrench it's probably the IWE's (hubs) and related to a fault in the vacuum system. If it sounds like marbles in a can, it's detonation. Both conditions are most likely to occur when you are fairly deep into the throttle.

 

The fact that it doesn't change with RPM leads me to basically rule out anything having to do with the engine.

If I assume that it is simply running out of vacuum, and the IWE system is partially engaged, is there any risk of damage if I just ignore it and let it click at me?

Your description of a ratchet wrench seems fairly accurate FWIW

 

Yes, you'll strip the splines out of the IWE's rather quickly. Then when you need 4wd it wont work.

 

Prob not related to your problem, but my 05 owners manual says DO NOT run anything but regular gas in it.