Cystic fibrosis is caused by inherited mutations in a single gene called CFTR, located on chromosome 7. A child must receive a defective copy of this gene from both parents to develop the disease. The CFTR gene controls a protein that moves chloride (a component of salt) in and out of cells, and when that protein is missing or broken, the body produces thick, sticky mucus that clogs the lungs, pancreas, and other organs.
How the CFTR Gene Works in Healthy Cells
The CFTR protein sits in the outer membrane of cells that produce mucus, sweat, saliva, tears, and digestive fluids. It acts as a tiny gate that lets chloride ions pass through the cell wall. This movement of chloride pulls water along with it, keeping the thin layer of liquid on organ surfaces properly hydrated. The result is mucus that flows freely and can be swept away by the hair-like cilia lining your airways.
The protein also helps regulate sodium channels in the same cells. In healthy lungs, this system is self-correcting: when the liquid layer on the airway surface gets too thin, sodium absorption slows down and chloride secretion ramps up, drawing water back to the surface. When the layer is too thick, the reverse happens. This constant balancing act keeps mucus at just the right consistency to trap bacteria and dust, then move them out of the lungs.
What Goes Wrong in Cystic Fibrosis
When both copies of the CFTR gene carry mutations, the chloride gate either never forms, falls apart before it reaches the cell surface, or sits in place but won’t open properly. Without functioning chloride transport, sodium absorption through neighboring channels runs unchecked. Cells pull too much salt inward, and water follows. The thin liquid layer coating the airways dries out, and the mucus sitting on top of it becomes thick, sticky, and acidic.
Dehydrated mucus is difficult for cilia to push upward. It stagnates, trapping bacteria and creating a breeding ground for chronic infection. Over time, repeated cycles of infection and inflammation damage the airway walls, causing permanent widening of the bronchial tubes. This same basic process, thick secretions blocking narrow passages, plays out across every organ that depends on CFTR.
The Inheritance Pattern
Cystic fibrosis follows an autosomal recessive pattern, meaning the mutated gene sits on a non-sex chromosome and you need two defective copies (one from each parent) to develop the disease. People who carry one working copy and one defective copy are called carriers. They produce enough functional CFTR protein to avoid symptoms and typically have no idea they carry the mutation.
When two carriers have a child, each pregnancy carries a 25% chance the child will have cystic fibrosis, a 50% chance the child will be a carrier without symptoms, and a 25% chance the child will inherit two normal copies. These odds reset with every pregnancy. They don’t change based on previous children’s outcomes.
The Most Common Mutation
More than 2,000 different CFTR mutations have been identified, but one dominates. Called F508del (sometimes written as Delta F508), this mutation deletes a single amino acid from the CFTR protein, causing it to misfold. The cell’s quality-control system recognizes the misshapen protein and destroys it before it ever reaches the cell surface. According to the Canadian Cystic Fibrosis Registry, about 90% of patients carry at least one copy of F508del, and half are homozygous, meaning they inherited this same mutation from both parents.
The remaining cases involve hundreds of rarer mutations that break the protein in different ways. Some prevent the gene from producing any protein at all. Others let the protein reach the cell surface but keep the gate locked shut, so chloride can’t pass through. Still others allow a partially working channel that conducts less chloride than normal, or produce a protein that functions briefly but gets pulled back inside the cell too quickly. These differences help explain why cystic fibrosis severity varies so widely from person to person. Two people with different mutation combinations can have markedly different disease courses.
How Thick Mucus Damages the Lungs
The lungs bear the heaviest burden. In healthy airways, a thin watery layer sits directly on top of the cells, with a gel-like mucus blanket floating above it. Cilia beat rhythmically in the watery layer, pushing the mucus blanket (along with any trapped particles) upward toward the throat. This self-cleaning system is called mucociliary clearance, and it runs continuously.
In cystic fibrosis, the watery layer is depleted because CFTR can’t secrete chloride and can’t restrain sodium absorption. Without enough liquid, the mucus blanket collapses onto the cilia, flattening them. They can no longer beat effectively. Bacteria that would normally be swept out in minutes now sit in place for hours or days, triggering an intense immune response. The inflammation itself causes further tissue damage, and over years this cycle of infection and inflammation is the primary driver of lung disease progression.
Effects on the Pancreas and Digestion
The pancreas produces digestive enzymes that normally flow through small ducts into the small intestine. CFTR dysfunction in the cells lining these ducts has three compounding effects: the secretions become more acidic (because the protein also helps transport bicarbonate, which neutralizes acid), lower in volume, and thicker due to concentrated proteins. This process begins before birth. Thick secretions plug the ducts, and the trapped digestive enzymes start breaking down the pancreatic tissue itself.
Over time, this leads to scarring and destruction of the enzyme-producing cells, a condition called pancreatic insufficiency. Without enough digestive enzymes reaching the intestine, the body struggles to absorb fats, proteins, and fat-soluble vitamins. This is why children with cystic fibrosis often have poor weight gain and nutritional deficiencies despite eating well. Roughly 85% of people with CF develop pancreatic insufficiency, though some milder mutations preserve enough pancreatic function to avoid it.
How Cystic Fibrosis Is Confirmed
Because the disease disrupts salt transport, the sweat glands of people with CF produce unusually salty sweat. The sweat chloride test measures the concentration of chloride in a sweat sample collected from the skin, usually the forearm. A chloride level of 60 mmol/L or higher is considered diagnostic. Results between 30 and 59 mmol/L fall into an intermediate range that requires further evaluation, often with genetic testing to look for specific CFTR mutations. A level of 29 mmol/L or below makes CF unlikely.
Most cases in the United States and many other countries are now detected through newborn screening, which checks for elevated levels of a pancreatic enzyme in the baby’s blood within the first few days of life. A positive screen is followed by sweat testing and, if needed, genetic analysis to confirm the diagnosis and identify the specific mutations involved. Knowing which mutations a person carries has become increasingly important because newer therapies target specific types of CFTR defects.