An increasing number of SIAH1 protein substrates have been authenticated, and they are mainly related to fundamental cellular processes, including hypoxia response pathways (AKAP1, HIPK2, FIH, and PHDs), DNA damage response (TIN2, TRF2, and HIPK2), and cancer inhibition (ACK1, PEG10, DX2, and TRAF4) [28–32]. The gene discussed is SIAH1; the disease is cancer.