CFTR stands for Cystic Fibrosis Transmembrane Conductance Regulator, a protein that acts as a channel on the surface of cells lining your lungs, pancreas, intestines, sweat glands, and reproductive organs. Its job is to move chloride and bicarbonate ions out of cells and into surrounding fluid, which pulls water along and keeps those surfaces properly hydrated. When the gene that codes for this protein is mutated, the result is cystic fibrosis, a serious inherited disease affecting roughly 1 in 3,000 people of European descent and around 70,000 people worldwide.
How the CFTR Protein Works
CFTR belongs to a large family of proteins called ABC transporters, which use cellular energy (ATP) to move molecules across membranes. Unlike most members of that family, CFTR functions as an ion channel rather than a pump. When the cell signals that chloride needs to leave, enzymes activate a regulatory section of the protein, and ATP locks two structural domains together to open the channel. Chloride flows out. When the ATP is broken down, those domains separate and the channel closes.
Chloride transport is only part of the picture. CFTR also lets bicarbonate pass through, and this matters in different ways depending on the organ. In the pancreas, bicarbonate neutralizes stomach acid so digestive enzymes can work. In the sinuses, it helps keep mucus thin and hydrated. In the male reproductive tract, it regulates the pH that sperm need to function. The protein is expressed across many tissues, which is why a single gene defect can cause problems in so many parts of the body.
The Gene Behind the Protein
The CFTR gene sits on chromosome 7 and spans a large stretch of DNA containing 27 coding segments (exons). It was identified in 1989, though the inheritance pattern for cystic fibrosis had been recognized decades earlier. CF follows an autosomal recessive pattern, meaning a child must inherit a faulty copy from each parent to develop the disease. People who carry one faulty copy and one working copy are carriers: they produce enough functional CFTR to stay healthy but can pass the mutation to their children.
More than 2,000 variants of the CFTR gene have been catalogued, but one mutation dominates. Called F508del, it accounts for roughly 90% of CF cases in Canada, with about half of patients carrying two copies of it. This single mutation deletes one amino acid from the protein, causing it to misfold inside the cell and get destroyed before it ever reaches the surface.
Six Classes of CFTR Mutations
Scientists group CFTR mutations into six classes based on what goes wrong at the cellular level. This classification matters because it determines which therapies can help.
- Class I: The cell never finishes building the protein. Premature stop signals in the genetic code halt production entirely.
- Class II: The protein is built but folds incorrectly. The cell’s quality-control system flags it as defective and breaks it down before it reaches the surface. F508del falls here.
- Class III: The protein reaches the cell surface but its gate doesn’t open properly, so ions can’t flow through.
- Class IV: The gate opens, but the channel pore is narrowed, reducing the amount of chloride that passes through.
- Class V: The protein is structurally normal but produced in smaller quantities due to errors in how the gene is read.
- Class VI: The protein works at the surface but is unstable, getting pulled back inside and recycled too quickly.
Classes I and II are generally the most severe because little to no functional protein ever reaches the cell surface. Classes III through VI tend to leave some residual function, which often translates to milder symptoms.
What Happens When CFTR Fails
The core problem is dehydration of the thin fluid layer that coats epithelial surfaces. In healthy airways, chloride flowing out of cells through CFTR creates an osmotic gradient that draws water after it, keeping the airway surface liquid thin enough for the tiny hair-like structures called cilia to sweep mucus and trapped bacteria upward and out. Without functional CFTR, that liquid layer shrinks. Mucus becomes thick and sticky, cilia get bogged down, and bacteria that would normally be cleared begin to colonize the lungs. Over time, repeated infections cause inflammation and scarring that progressively destroy lung tissue.
The lungs get the most attention, but other organs suffer too. In the pancreas, thick secretions block the ducts that deliver digestive enzymes to the intestine, leading to malnutrition and, eventually, scarring of the pancreas itself. Some of this damage begins before birth. The sweat glands work in reverse: CFTR normally reabsorbs chloride from sweat as it travels through the duct, so people with CF lose excessive salt in their sweat. The intestines can become obstructed, and in nearly all males with CF, the vas deferens (the tube that carries sperm) fails to develop properly, causing infertility.
How CF Is Diagnosed
Most cases are now caught through newborn screening, which checks for elevated levels of a pancreatic enzyme in the blood. Babies who screen positive are referred for a sweat chloride test, the gold standard for CF diagnosis. A small amount of sweat is collected, usually from the forearm, and the chloride concentration is measured. A result of 60 mmol/L or higher confirms CF. Values of 29 mmol/L or below are normal. The intermediate range, 30 to 59 mmol/L, requires further evaluation including genetic testing.
Some infants fall into a gray zone: they have elevated screening markers and carry two CFTR mutations, but at least one of those mutations isn’t definitively known to cause CF, and their sweat chloride is normal or borderline. These babies are given the designation CFTR-related metabolic syndrome (CRMS). They don’t meet the criteria for a CF diagnosis, but they need ongoing monitoring because some will develop CF-related problems over time while others will remain healthy.
CFTR Modulator Therapies
For decades, CF treatment focused on managing symptoms: clearing mucus, fighting infections, and supplementing digestive enzymes. Starting in 2012, a new category of drugs called CFTR modulators began targeting the underlying protein defect. These drugs work in two fundamentally different ways.
Potentiators help CFTR channels that reach the cell surface but don’t open correctly. Ivacaftor, the first potentiator approved, increases chloride flow through the channel and works well for Class III gating mutations. Correctors, on the other hand, help misfolded proteins (like those from the F508del mutation) fold properly so they can travel to the cell surface in the first place.
The biggest breakthrough came with a triple combination therapy that pairs two correctors with ivacaftor. Each corrector binds to a different spot on the misfolded CFTR protein, and together they rescue enough protein to meaningfully restore chloride transport. This combination is approved for anyone with at least one copy of the F508del mutation, which covers the vast majority of CF patients. Clinical improvements have been dramatic: better lung function, fewer hospitalizations, and significant weight gain.
Not everyone benefits equally. Patients with Class I mutations, where no protein is produced at all, have nothing for correctors or potentiators to work on. For these individuals, the median survival remains substantially lower, possibly by more than a decade compared to those who can take modulators.
Life Expectancy Today
The outlook for people born with CF has changed enormously. According to the Cystic Fibrosis Foundation’s 2024 registry data, children born with CF between 2020 and 2024 have a predicted median survival of 65 years or beyond. That figure reflects the cumulative impact of newborn screening, specialized care centers, better infection management, and CFTR modulator therapy. The historically lower survival among females has also narrowed significantly and is now only slightly below that of males. These are population-level predictions, though, and individual outcomes vary based on mutation type, access to modulators, and other health factors.