UBX domain-containing protein 6

UBXN6 (UBX domain-containing protein 6) is a VCP cofactor that negatively regulates the ATPase activity of VCP, an ATP-driven segregase involved in diverse cellular processes (UniProt: Q9BZV1). As a VCP-associated factor, UBXN6 participates in protein quality control pathways, including endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins and macroautophagy-mediated clearance of damaged lysosomes. It also facilitates transport of CAV1 to lysosomes for degradation.

UBXN6 is expressed in human tissues and functions within cellular protein homeostasis and autophagy networks (UniProt: Q9BZV1). No disease associations are annotated in UniProt curated databases. The protein operates primarily in intracellular compartments involved in protein quality control and degradation pathways.

UBXN6 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.45. This reduction was observed in human post-mortem AD brain analyzed by quantitative proteomics across subcellular fractions. The decreased abundance may reflect impaired protein quality control capacity in the AD brain microenvironment.