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Over the past two decades, a multistep process has been proposed to explain amyotrophic lateral sclerosis (ALS) pathogenesis, implicating genetic factors, environmental exposures and time.1 These models require validation through robust clinical and biological measures of disease state and progression. To this end, biomarkers such as neurofilament light chain (NfL) have taken centre stage in integrating data for clinical risk prediction and insights into disease biology. NfL is reliably and reproducibly measured in both cerebrospinal fluid (CSF) and blood, offering unprecedented sensitivity for ALS stratification based on phenotypes, such as progression rate.2 It signals disease onset and the prodromal phase in asymptomatic, genetically at-risk individuals and may also provide an early biological indication of treatment response.3 NfL changes most likely reflect both functional changes and structural breakdown of neurons and axons.