While neuronal and glial cytoplasmic inclusions of the 43 kDa transactive response DNA-binding protein, TDP-43, are common to 97% of cases of ALS (across disparate monogenetic and apparently sporadic cases), there have been very few postmortem studies of PLS in the modern era of immunohistochemistry.6 7 Debate as to whether PLS represents an extreme end of a continuum with ALS, or a distinct disorder is ongoing. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.