SPOP mutations occur 10–15% of Pca (prostate adenocarcinoma)11,14–16, which have been found to be present predominantly in the substrate-binding MATH domain; such mutations inactivate SPOP’s function by disrupting SPOP-substrate interactions, thereby altering the steady-state levels of key components in the AR signaling pathway and contributing to PCa development8,17. The gene discussed is SPOP; the disease is prostate adenocarcinoma.