In echoing the tumor suppressor roles of SPOP, growing body of evidence show that substrates of SPOP, such as AR [21], steroid receptor coactivator 3 (SRC-3) [22], DEK proto-oncogene (DEK) [23], tripartite motif containing 24 (Trim24) [15], ETS related gene 1 (ERG) [24], bromodomain-containing protein 4 (BRD4) [25] and proto-oncogene c-Myc (c-MYC) [26], play malignant roles in the consequence of SPOP loss-of-function mutations in PrCa. The gene discussed is NCOA3; the disease is neoplasm.