Hey everyone, today I want to upgrade our mental model of PKD with a reframe.

As you know, a mutation is an error in our genetic code. This code gets read and turned into proteins. And proteins are literal tiny machines that do physical work in our bodies — moving things, pumping fluid, etc.

In PKD, two genes (PKD1 and PKD2) make two proteins usually called polycystin-1 (PC1) and polycystin-2 (PC2). Those names describe the symptom of cysts in the kidneys — or essentially what goes wrong when these proteins are not doing their job — not what they actually do. That’s like calling a car an “explosion machine” because it could explode if misused. Totally not helpful.

Now, how about a better name that truly describes their function?

Let’s use: Calcium Level and Epithelial Adhesion Regulator (CLEAR) 1 and 2.

CLEAR1 = PC1.
CLEAR2 = PC2.

(Epithelial meaning outer surface, for example of organs like the kidney.)

Why CLEAR? Because these proteins help regulate calcium inside the cell and also regulate how much cells stick together (adhesion).

When CLEAR1/2 are low (as in PKD1/PKD2), two big things happen:

1. Lower intracellular calcium → lower energy.
   Calcium is needed for our mitochondria to make energy.
2. Weaker epithelial adhesion → leaky barriers.
   Cells don’t hold together as tightly, so more “stuff” like toxins seeps between cells — both in the gut lining and in the kidney tubules.

Put those together and you get a body starting with less cellular energy for detox, plus more junk ending up between cells where it doesn’t belong. Over time, the body encapsulates what doesn’t belong — leading to cysts.

If you understand that PKD is truly nothing else than a CLEAR1 or CLEAR2 deficiency, you start asking better questions:

• Does this choice strengthen epithelial adhesion / barrier integrity (gut and kidney)?
• Does it improve cellular energy so the system can repair?
• Does it improve detoxification?

Now, ketones actually only act on this whole process afterwards. When the cysts are already forming in a low-energy state, unable to detox, this ramps up glucose uptake — and this is what we can inhibit with a ketogenic diet, pumping the brakes on this out-of-control growth.

The CLEAR model gives us a better understanding of how to improve our chances upstream — by closing barriers as much as possible and optimizing mitochondrial function — so the loss of some percentage of CLEAR is not as problematic as it would otherwise be.

– Felix