YOD1 deubiquitinase (YOD1)

YOD1 deubiquitinase is a cysteine protease enzyme belonging to the OTU (ovarian tumor domain) family of deubiquitinating enzymes. It plays a central role in *cellular protein quality control* by removing ubiquitin chains from specific substrates, facilitating the degradation of misfolded proteins via the endoplasmic reticulum-associated degradation (ERAD) system. YOD1 is also critical in autophagy, particularly in clearing damaged lysosomes by processing K48-linked ubiquitin chains. It regulates multiple signaling pathways: negatively modulates NF-κB signaling by interacting with TRAF6, suppresses MAVS aggregation in antiviral responses, and acts as a pivotal regulator of the Hippo pathway by deubiquitinating and stabilizing ITCH (an E3 ligase), leading to downstream YAP/TAZ activation and cellular proliferation. High YOD1 expression is implicated in *liver cancer* and is a promising therapeutic target for modulating Hippo pathway activity. Alternative splicing of the gene produces multiple isoforms.

Other names

YOD1OTU domain-containing protein 1OTUD2OTU1

Drugs targeting YOD1 would typically act via *DUB inhibition* (blocking cysteine protease activity), leading to accumulation of ubiquitinated substrates, impaired autophagy, altered signaling through Hippo, NF-κB, or antiviral pathways. Modulation via microRNA (miR-21) downregulates YOD1 protein translation, affecting Hippo pathway signaling and cell proliferation.