TUBA4A and amyotrophic lateral sclerosis: Impaired dimerisation and microtubule instability are shared functional defects of most mutant tubulin proteins, including TUBA4A mutants.7,16–19 However, these gain-of-function pathomechanisms, primarily due to missense variants, can lead to vastly different phenotypes.7,12 Additionally, heterozygous protein truncating variants in TUBA4A, which escape nonsense-mediated decay and result in loss of parts of C-terminal TUBA4A, ultimately forming a shorter protein, have also been associated with ALS and FTD phenotypes.7,20