For instance, the DDB1-DDB2-CUL4-RBX1 (CRL4DDB2) E3 ubiquitin ligase consists of damage-specific DNA-binding protein 1 (DDB1), damage-specific DNA-binding protein 2 (DDB2), cullin 4A (CUL4A), and RING-box protein 1 (RBX1), which exerts critical roles in various diseases such as cancers by mediating the ubiquitination and degradation of various proteins including histones H2A, H3, H4, progestin and adipoQ receptor 3 (PAQR3), and p27 18. The gene discussed is CUL4A; the disease is cancer.