Tight control of XPC ubiquitination is likely required to ensure DNA repair but may be dysregulated in human cancers, including lung cancers, which have been shown to have high levels of ubiquitin ligases, such as Cullin-RING ubiquitin ligase 4 A (CUL4A), overexpression of which is common in cigarette smoke-related lung cancer, and which is inversely proportionate to XPC expression (26). The gene discussed is CUL4A; the disease is lung cancer.