The authors showed a reduction of TJ proteins (ZO-1, occludin, and claudin-5), detection of microhemorrhages with the release of neurotoxic hemoglobin-derived products (hemosiderin), and IgG leakage in the pre-symptomatic stage of SOD1 mutant animals, suggesting vascular alterations as an early ALS pathological event. The gene discussed is CLDN5; the disease is amyotrophic lateral sclerosis.