Finally, recent discoveries that axonal guidance and collapse pathways may be triggered near vulnerable ALS neuromuscular junctions and other serendipitous findings that the CRMP2/CRMP4 system is perturbed in ALS may point to an unexpected and exciting new concept in ALS therapy: rational pharmacological manipulation of cytoskeletal restructuring pathways to support the structure and function of motor axons. Here, DPYSL2 is linked to amyotrophic lateral sclerosis.