Nuclear protein localization protein 4 homolog (NPLOC4)

Nuclear protein localization protein 4 homolog (NPLOC4) is a ubiquitin recognition adaptor that binds to polyubiquitinated proteins and, as part of the VCP (p97)–UFD1–NPLOC4 ATPase complex, mediates their extraction from cellular compartments for proteasomal degradation[1][2][3][4][5][6]. NPLOC4 is essential for processes including ER-associated protein degradation, mitotic spindle disassembly, nuclear envelope formation, and negative regulation of innate immune signaling (RIG-I, interferon production)[3][4]. Structural analyses reveal its engagement with several protein domains—chiefly a zinc finger, MPN, UBX-like, and NZF domains—that underpin substrate recognition and interaction with binding partners[2]. NPLOC4 dysregulation is implicated in cancer pathogenesis and neurodegenerative disorders, and it is emerging as a biomarker and target for therapeutic intervention, notably in the context of drugs that disrupt protein homeostasis, such as disulfiram/copper complexes[1]. If further structured data is required for specific clinical trials, genetic variants, or pathway maps, these can be retrieved in subsequent queries using resources like UniProt (Q8TAT6), OMIM (606590), or relevant cancer genomics platforms[3][4].

Other names

NPL4NPLOC4KIAA1499FLJ20657Ubiquitin recognition factor NPL4Nuclear protein localization 4 homolog

For drugs (e.g., disulfiram/copper): Inhibition of NPLOC4-p97 complex, leading to impaired proteasomal substrate processing and increased apoptosis in cancer cells - Modulation of substrate unfolding and extraction, impacting ERAD and cell survival pathways