MAPT and amyotrophic lateral sclerosis: In this review, we will discuss the nature of the phenotypic heterogeneity of ALS as it applies to associated syndromes of frontotemporal dysfunction that can be associated with ALS, explore the nature of the proteinopathies that are thought to underlie the process including a critical analysis of perturbations in microtubule associated protein tau (tau) metabolism, and consider a conceptual framework in which synergism amongst co-expressed toxic proteins can drive disease phenotype.