mRNA of ZO-1 and occludin are decreased in sporadic and familial cases of ALS.101 The NVU is further impaired by misplaced astrocytic end feet and decreased basement membrane formation due to reduced collagen IV.62,108 Basement membrane damage due to reduced collagen can be seen directly in the ventral horns of the spinal cord, exemplifying its profound role in MN damage and ALS pathology.109 BCNSB permeability is clearly recognized preclinically as well as clinically, but further unveiling of the pathophysiology is needed to develop effective treatments. This evidence concerns the gene OCLN and amyotrophic lateral sclerosis.