Amyotrophic lateral sclerosis (ALS) is classified in sporadic forms (sALS) present in 90 % of the cases and familial forms (fALS) present in the remaining 10% of the cases. Both forms are characterized by the presence of intracellular aggregates. sALS and fALS, except those related to Superoxide Dismutase 1 (SOD1), are characterized by inclusions positive for TAR-DNA binding protein 43 (TDP-43). These inclusions sequester essential cellular components and could impair the Protein Control Quality (PQC) system. The PQC system can also be altered by the mutation of genes that express proteins involved in the system. One of the genes found mutated in fALS is Valosin Containing Protein (VCP). VCP is a member of the AAA+ ATPase family that are chaperon-like proteins involved in the PQC system. VCP works as a homohexamer and contains two ATPase units and an N-terminal unit. The N-terminal unit interacts with a large number of adaptors that permits VCP to be involved in various pathways of the PQC system. VCP role is to route misfolded proteins mainly to the Ubiquitin Proteasome System (UPS) but recently VCP was found involved also in the autophagic pathway. Recent studies show that in VCP-ALS patients, as well as in other diseases where VCP is found mutated, the brain tissue is characterized by inclusions positive for TDP-43. Experimental work also correlated VCP-mutants to the impairment of the autophagic pathway, suggesting an involvement of VCP in the clearance of intracellular inclusion and its impairment in disease. Here we report that the overexpression of VCP in an ALS in vitro model enhances the clearance of mutated SOD1-aggregates mainly through the UPS. Moreover, VCP seems to have a role also in the removal of TDP-43 aggregates. In fact the chemical inhibition of VCP increases the aggregation of TDP- 43. These data start to define VCP importance in the clearance of misfolded protein aggregates, which are the cause of cell-toxicity in ALS and other neurodegenerative diseases. These findings could make VCP a new potential target for ALS.