Neurofilaments are axonal cytoskeletal proteins found in the CSF and blood in a wide range of central nervous system disorders, with levels broadly linked to the rate of disease progression.5 In ALS, studies spanning more than two decades have correlated neurofilament light chain (NFL) levels with the rate of both disability accrual, as measured by the decline in the ALSFRS-R, and with overall survival.6–8 Individual longitudinal CSF NFL levels appeared relatively stable over time,9 making it a candidate pharmacodynamic marker of rate of disease progression in therapeutic trials.10 The gene discussed is NEFL; the disease is central nervous system disorder.