Ubiquitin thioesterase OTU1

YOD1 (ubiquitin thioesterase OTU1) is a deubiquitinating enzyme that removes conjugated ubiquitin from protein substrates (UniProt: Q5VVQ6). It participates in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins and may facilitate substrate threading through the VCP/p97 pore by trimming ubiquitin chains. The enzyme also plays a role in macroautophagy, potentially recruiting VCP and other factors to damaged lysosomes to remove K48-linked ubiquitin chains and promote autophagosome formation.

YOD1 is expressed broadly but has particular relevance to cellular protein quality control and autophagy pathways. UniProt reports no established disease associations for this protein.

In Alzheimer's disease, YOD1 is downregulated in post-mortem human AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.76 (Chaparral AD proteomics). This reduced expression may impair protein quality control mechanisms and autophagy-dependent clearance of damaged organelles, potentially contributing to the pathological protein accumulation characteristic of AD neurodegeneration.