Hence, it is possible that TDP-43 APA of MARK3 promotes increased tau S262 phosphorylation by shifting the subcellular localization of MARK3 protein, indicating that TDP-43 APA of MARK3 may contribute to tau dysregulation and altered cytoskeletal dynamics in TDP-43 proteinopathies, even in the absence of overt tau pathology. This evidence concerns the gene TARDBP and proteostasis deficiencies.