VAPB and amyotrophic lateral sclerosis: VapB mutation reduces Smad2/3, which are central mediators of TGF-β, and impairs BMP/TGF-β signaling.25 Another gene that influences both ALS and TGF-β pathway is zinc finger protein 512B, which codes for a transcription factor that has been established as a prognostic factor in ALS.26 Mice and zebrafish models of ALS suggest that the gdf6a mutation in the GDF6 gene could enhance the phenotypes of motoneuron and neuronal degeneration.11 A mutation in GDF6 was also found in autosomal-dominant KFS1.