PTK2 plays a critical role in proteinopathies as it favors abnormal phosphorylation of proteins, including TDP-43 and p62/SQSTM1 leading to the formation of ubiquitinated aggregates and neurotoxicity induced by the dysregulation of the ubiquitin–proteasome system (UPS; Lee et al., 2020b). Here, TARDBP is linked to proteostasis deficiencies.