For instance, the quantity and ratio of proteasome forms (constitutive proteasomes vs. immunoproteasomes) in tumor cells can predict the clinical effects of broad specificity proteasome inhibitors (99, 282), which target both the constitutive and immune catalytic subunits of 20S proteasomes and represent major UPS-directed anti-cancer drugs that are used in clinics (17, 98). The gene discussed is HMBS; the disease is cancer.