So, what happens when someone loses 100 pounds and keeps it off for a lifetime? What happened when a 200 lb person becomes 100 lbs? How have they defied the setpoint?

They did something that changed the setpoint.

Somewhere between 33% and 67%? So, somewhere between most people succeed at dieting and most people fail.

If you define success at dieting at not increasing your weight, I think you have different standards than most people.

I'm curious, what do you suggest for a general ELI5 weight loss plan? If someone weighs 200 lbs and decides they want to reduce their BMI to within a healthy range and get down to 150 lbs, how shall they proceed?

I don't have the data to proof that a certain recommendation is the best, but ideas I consider to be promising are: 1) Check whether something like a virus produces unnecessary inflamation and fight the virus if there's one. 2) Shangri La diet. 3) Hackers diet style charting. 4) Work through the surrounding psycholoigcal issues with a good hypnotherist or otherwise skilled person.

I don't think the tricks from 2 to 4 are enough when the core reason is an illness that produces inflamation. Different people are likely overweight for different reasons and there won't be a one-size-fits-all solution.