ΔF508

All right, so they don't ever get it.

So you think of Delta F508 as being your classic, your most common mutation, and that protein has two kinks in it.

And it gets stuck in the endoplasmic reticulum where it builds up and causes damage, right? So the first drugs that came out were actually the potentiators.

And so that was Ivacaftor or Klydeco.

So each mutation has a different issue with the sodium, like where it's entering, if it's not entering, if it's not staying up in the cells.

I have, I'm a double Delta F508, which I think is hilarious because I sound like an airplane working in travel.

Okay, yeah.

And my salt proteins just don't stay up.

And this gen-genetic diversity explains why disease severity can vary so considerably between patients.

The most common mutation is known as F508del and results in abnormal protein folding and premature degradation before the protein reaches the cell surface.

And it was understanding this mechanism that laid the foundations for today's CFTR modulator therapies, arguably one of the most important advances in respiratory medicine over the past decade.

The lungs illustrate the consequences of CFTR dysfunction particularly well, I think.