In contrast, there are examples of ALS-causing mutations, occurring in a minority of cases and typically with a lower motor neuron phenotype, such as in dynactin subunit 1 [19], the actin-binding protein profilin-1 [20], the microtubule subunit TUBA4A [21] and the kinesin motor protein KIF-5A [22], which point to cytoskeletal and axonal defects as a contributor to ALS pathology and which have a more obvious relationship to the characteristic function of the protein. Here, PFN1 is linked to amyotrophic lateral sclerosis.