ATP-dependent chaperone which probably uses the energy provided by ATP hydrolysis to generate mechanical force to unfold substrate proteins, disassemble protein complexes, and disaggregate protein aggregates (PubMed:21454554, PubMed:31445887). By recruiting and promoting the degradation of ubiquitinated proteins, plays a role in the ubiquitin fusion degradation (UFD) pathway (PubMed:16428438). Has a role in the endoplasmic reticulum-associated degradation (ERAD) pathway which mediates the cytoplasmic elimination of misfolded proteins exported from the ER (PubMed:11813000, PubMed:11740563, PubMed:11847109, PubMed:21148305). Required for the proteasome-dependent processing/activation of MGA2 and SPT23 transcription factors leading to the subsequent expression of OLE1 (PubMed:11847109, PubMed:11733065). Has an additional role in the turnover of OLE1 where it targets ubiquitinated OLE1 and other proteins to the ERAD (PubMed:11847109). Regulates ubiquitin-mediated mitochondria protein degradation (PubMed:21070972, PubMed:27044889). Involved in spindle disassembly probably by promoting the degradation of spindle assembly factors ASE1 and CDC5 at the end of mitosis (PubMed:14636562). Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:23178123, PubMed:24261871). CDC48 may provide the mechanical force that dislodges the polyubiquitinated nascent peptides from the exit channel (PubMed:23178123, PubMed:24261871). Required for ribophagy, a process which relocalizes ribosomal particles into the vacuole for degradation in response to starvation (PubMed:20508643). Component of the DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions and support a role in protein quality control (PubMed:29355480). Substrate initially binds through the attached polyubiquitin chain to UDF1/NPL4 and then moves through the pore of the ATPase rings and is thereby unfolded (PubMed:31249135, PubMed:31249134). Acts on a broad range of even well-folded proteins via ubiquitin-binding and unfolding to initiate substrate processing (PubMed:31249135). Involved in degradation of mislocalized tail-anchored transmembrane proteins extracted from the mitochondrion outer membrane by MSP1 and ubiquitinated by DOA10 (PubMed:31445887). ATP + H2O = ADP + H(+) + phosphate The first ATP-binding region has low ATPase activity (By similarity). The second ATP-binding region is responsible for ATPase activity (By similarity). ATP binding to the first ATP-binding region induces intrinsic activity of the second ATP-binding region (PubMed:21454554). While ATP binding to the first ATP-binding region appears to prevent ATP hydrolysis by the second ATP-binding region, ADP-binding to first region promotes the coordinate and cooperative ATPase cycle of the second ATP-binding region (By similarity). ATP binding to the first ATP-binding region induces a conformational change, promoting the rotation of the first ATP-binding region relative to the second ATP-binding region in the hexamer (By similarity). Component of the heterotrimeric CDC48-NPL4-UFD1 ATPase complex (PubMed:16873066). The CDC48-NPL4-UFD1 ATPase complex interacts with the HRD1 ubiquitin ligase complex composed of the E3 ligase HRD1, its cofactors HRD3, USA1 and DER1, substrate recruiting factor YOS9 and CDC48-binding protein UBX2 (PubMed:16873066). Interaction between the complexes is mediated by interaction between CDC48-NPL4-UFD1 complex member CDC48 and HRD1 complex member UBX2 (PubMed:16873066). Forms a complex composed of CDC48, NPL4, UFD1, UFD2 and SHP1 (PubMed:16427015). Forms a complex composed of CDC48, NPL4, UFD1, DOA1, SHP1 and deubiquitinase OTU1; within the complex interacts with DOA1/UFD3 and OTU1 to prevent multiubiquitination of substrates (PubMed:16427015). Interacts with UFD2, to add further ubiquitin moieties; the interaction with UFD2 is prevented by DOA1/UFD3 (PubMed:16427015). Forms a complex composed of CDC48, DOA1, deubiquitinase UBP3 and probably BRE5; within the complex interacts with DOA1 and UBP3 (PubMed:20508643). Interacts (via C-terminus) with DOA1 (via PUL domain); the interaction is direct (PubMed:16428438, PubMed:19805280, PubMed:27044889). Interacts with NPL4 (PubMed:11733065, PubMed:11598205, PubMed:31249134). Interacts with SHP1/UBX1, UBX2, UBX3, UBX4, UBX5, UBX6 and UBX7 (PubMed:15258615, PubMed:31249134). Interacts with VMS1; the interaction recruits CDC48 to the mitochondria in response to mitochondrial stress (PubMed:21070972, PubMed:21148305). Component of the ribosome quality control complex (RQC), composed of the E3 ubiquitin ligase RKR1/LTN1, RQC1 and RQC2, as well as CDC48 and its ubiquitin-binding cofactors (PubMed:23178123, PubMed:23479637). RQC forms a stable complex with 60S ribosomal subunits (PubMed:23178123, PubMed:23479637). Interacts with ASE1 and CDC5; the interaction is likely to result in their degradation (PubMed:14636562). Component of the DSCc E3 ligase complexes composed of at least TUL1, DSC2, DSC3, UBX3, CDC48 as well as VLD1 for the vacuole-localized complex or GLD1 for the Golgi/endosome-localized complex (PubMed:29355480). Bound loosely to components of the microsomal fraction. Present with 78400 molecules/cell in log phase SD medium. Belongs to the AAA ATPase family.