Highlighting the relevance for ubiquitin signaling in organism homeostasis, mutations in RING E3s are frequently associated with human diseases such as BRCA1 (breast cancer type 1 susceptibility protein) mutations in patients with breast and ovarian cancer (Hashizume et al., 2001; Ruffner et al., 2001), and MDM2 (mouse double minute 2 homolog) amplification in several human cancers (Oliner et al., 1992; Wade et al., 2010). The gene discussed is BRCA1; the disease is cancer.