The study investigates the link between a mutation in the *DCTN1* gene, which encodes the p150 subunit of dynactin, and lower motor neuron disease. Dynactin is a key protein involved in axonal transport, and its dysfunction has been implicated in motor neuron degeneration. The researchers identified a single-base-pair change (G59S) in the *DCTN1* gene, which results in an amino-acid substitution at position 59. This mutation is predicted to distort the folding of dynactin's microtubule-binding domain, leading to decreased binding to microtubules. Binding assays confirmed that the mutant protein has reduced affinity for microtubules compared to the wild-type. The findings suggest that impaired axonal transport, specifically through dysfunction of dynactin-mediated transport, can contribute to human motor neuron disease. The study also highlights the potential role of other members of the dynactin–dynein complex in motor neuron degeneration and opens avenues for further research into the mechanisms underlying this disease.The study investigates the link between a mutation in the *DCTN1* gene, which encodes the p150 subunit of dynactin, and lower motor neuron disease. Dynactin is a key protein involved in axonal transport, and its dysfunction has been implicated in motor neuron degeneration. The researchers identified a single-base-pair change (G59S) in the *DCTN1* gene, which results in an amino-acid substitution at position 59. This mutation is predicted to distort the folding of dynactin's microtubule-binding domain, leading to decreased binding to microtubules. Binding assays confirmed that the mutant protein has reduced affinity for microtubules compared to the wild-type. The findings suggest that impaired axonal transport, specifically through dysfunction of dynactin-mediated transport, can contribute to human motor neuron disease. The study also highlights the potential role of other members of the dynactin–dynein complex in motor neuron degeneration and opens avenues for further research into the mechanisms underlying this disease.