VEGFA and amyotrophic lateral sclerosis: The genes can be predominantly categorized into four disease-associated mechanisms: (i) protein trafficking, stability and degradation, (ii) RNA processing and nuclear export/import, (iii) cytoskeletal and axonal function and (iv) mitochondrial function, with only minor exceptions (e.g. VEGFA).21,46 Furthermore, many ALS-associated genes affect cellular function mainly or partially via a loss-of-function mechanism (Supplemental Table 1).