ALS has no single cause—most cases appear to be a mix of genetic and environmental factors working together

About 90 percent of ALS cases have no known family history, meaning they appear to start randomly in a person rather than being inherited. These are called sporadic ALS. The remaining 10 percent run in families and are called familial ALS. In both types, something goes wrong with the motor neurons—the nerve cells that control your muscles—but researchers have not pinned down exactly why this happens in most people.

What we do know is that ALS involves a combination of things: genes you carry, exposures in your environment or work, possibly infections, and random cellular damage that accumulates over time. No single factor causes it. A person might carry a genetic risk but never develop ALS. Another person with no family history might develop it anyway. This is why ALS remains difficult to predict and prevent.

Key Takeaways

  • Most ALS cases (90 percent) are sporadic, meaning they do not run in families, and the exact cause remains unknown.
  • Familial ALS accounts for about 10 percent of cases and is linked to inherited gene mutations, most commonly in the SOD1, C9orf72, and FUS genes.
  • Environmental and occupational exposures—including heavy metals, pesticides, military service, and intense physical activity—are suspected risk factors but have not been proven to cause ALS on their own.
  • Motor neurons die or malfunction in ALS, but why this happens involves multiple factors acting together rather than one clear cause.
  • Research continues into inflammation, protein buildup, and other cellular processes that may explain why motor neurons fail.

Genetic mutations linked to familial ALS

When ALS runs in families, it is usually because of a mutation in one of several genes. The most common is SOD1, found in about 20 percent of familial cases. Other frequent mutations occur in C9orf72 and FUS. Each of these genes normally helps protect or maintain motor neurons. When mutated, they appear to allow neurons to break down or become toxic.

If one of your parents carries a familial ALS mutation, you have roughly a 50 percent chance of inheriting it. However, inheriting the mutation does not may provide you will develop ALS—some people carry it their whole lives without symptoms. This is called incomplete penetrance, and it shows that genes alone do not determine whether ALS appears.

Genetic testing can identify these mutations, but it is not routine for everyone with ALS. Testing is most useful if you have a family history of the disease or if you are considering having children and want to know your genetic status. A genetic counselor or neurologist can discuss whether testing makes sense for your situation.

Environmental and occupational exposures under investigation

Researchers have noticed that certain groups develop ALS at higher rates, which suggests environmental factors play a role. Military veterans, particularly those deployed to the Gulf War, have higher ALS rates than the general population. People who work with pesticides, heavy metals, or solvents also show elevated risk. Intense physical activity and athletic careers have been associated with ALS in some studies, though the connection is not fully understood.

Lead, mercury, and other heavy metals have been found in higher concentrations in some people with ALS, but it is unclear whether exposure caused the disease or whether the disease process itself changes how metals accumulate in the body. Pesticide exposure is suspected but not proven. The problem is that ALS takes years or decades to develop, so it is hard to connect a specific exposure from 20 years ago to symptoms today.

None of these exposures have been shown to cause ALS on their own. Rather, they may increase risk in people who are already genetically vulnerable. This is why two people with identical pesticide exposure may have very different outcomes.

Protein buildup and cellular damage in motor neurons

Inside motor neurons, researchers have found abnormal accumulations of proteins, particularly TDP-43 and SOD1. These proteins clump together instead of breaking down normally, and the buildup appears toxic to the cell. The neuron cannot clear out the damaged proteins, so they pile up and eventually the cell dies.

This process is similar to what happens in other neurodegenerative diseases like Parkinson's and Alzheimer's, but the specific proteins involved differ. In ALS, the motor neurons seem especially vulnerable to this kind of protein damage, though we do not yet know why motor neurons are targeted while other nerve cells are spared.

Researchers are studying whether inflammation, oxidative stress (cellular damage from unstable molecules), and problems with how cells produce energy all contribute to this protein buildup. It is likely that multiple processes go wrong at once, rather than a single broken mechanism.

Why some people develop ALS and others do not

The fact that identical twins do not always both develop ALS, and that people with the same genetic mutation sometimes never get sick, tells us that something beyond genes determines who develops the disease. This "something" might be a second genetic factor, an environmental trigger, random cellular damage, or a combination of all three.

One theory is that ALS requires a second hit—a person is born with genetic vulnerability, but then something else happens (an infection, an injury, an exposure, or just bad luck with cell damage) that tips them into disease. Another theory is that the disease is triggered by a rare combination of factors that only some people experience.

This uncertainty is why prevention is so difficult. There is no proven way to avoid ALS if you carry a genetic risk, and no clear exposure to avoid if you do not have genetic risk. The best current advice is general health maintenance: manage cardiovascular health, avoid known toxins when possible, and stay physically active in moderate ways.

What researchers are still trying to understand

Major research efforts are focused on understanding why motor neurons fail in ALS while other neurons survive. Scientists are investigating whether the immune system attacks motor neurons, whether problems with cell-to-cell communication play a role, and whether defects in how cells dispose of waste contribute to neuronal death.

Studies are also examining whether certain infections—particularly viruses—might trigger ALS in vulnerable people. Other research looks at whether problems with the blood-brain barrier (the protective layer around the brain and spinal cord) allow harmful substances to reach motor neurons.

The reason ALS research has not yet produced a cure or prevention strategy is that the disease appears to result from multiple different problems happening in the same cells. Two people with ALS might have different underlying causes, which is why a treatment that works for one person may not work for another.

Frequently Asked Questions

Is ALS inherited or can you catch it?

ALS is not contagious. About 10 percent of cases are inherited through families via gene mutations. The other 90 percent appear randomly and are not passed down, though researchers believe genetic factors still play a role in sporadic cases—just not in a way that runs in families.

If my parent has ALS, will I definitely get it?

No. If your parent has familial ALS caused by a gene mutation, you have about a 50 percent chance of inheriting that mutation. But inheriting the mutation does not may provide you will develop symptoms. Some people carry the mutation their entire lives without ever getting sick.

Can stress or physical injury cause ALS?

There is no evidence that stress or a single injury causes ALS. Some studies suggest that intense, prolonged physical activity may be associated with higher risk in certain people, but this is not proven and does not mean exercise causes the disease in most cases.

Does living near power lines or using cell phones cause ALS?

No. Multiple large studies have found no link between electromagnetic fields from power lines or cell phones and ALS risk. These are common concerns, but the scientific evidence does not support them as causes.

Can ALS be prevented if I know I carry a gene mutation?

Currently, there is no proven prevention strategy for people who carry ALS gene mutations. Maintaining overall health, managing cardiovascular fitness, and avoiding known toxins when possible are reasonable general practices, but they have not been shown to prevent ALS in mutation carriers.