The reversibility of ubiquitination is maintained by deubiquitinating enzymes, which remove ubiquitin from proteins.[71] Disruptions in ubiquitination pathways are closely linked to diseases such as cancer, neurodegenerative disorders, and immune dysfunctions.[72] For instance, POH1, identified as a novel deubiquitinase for Smad3, enhances TGF‐β1/Smad3 signaling and promotes metastasis in lung adenocarcinoma by stabilizing Smad3 (Figure 4E).[73]. The gene discussed is SMAD3; the disease is cancer.