Speckle-type POZ protein (SPOP) is a tumor suppressor of PCa and functions as a substrate receptor of the Cullin 3 (CUL3)-based ubiquitin ligase.1–4 CUL3SPOP directs ubiquitin-proteasomal degradation of key regulators, e.g., DEK Proto-Oncogene (DEK), Bromodomain Containing 4 (BRD4), Programmed Cell Death Protein 1 (PD1) including AR, and AR co-activators Nuclear Receptor Coactivator 3 (SRC-3) and Tripartite Motif Containing 24 (TRIM24)1,3,5,6of the AR signaling pathway. The gene discussed is CUL3; the disease is neoplasm.