Approximately one in eight men will be diagnosed with prostate cancer in his lifetime. Prostate cancer is commonly androgen addicted, in which case androgen receptor signal inhibitors (ARSI) can prolong survival. However, the cancer cells eventually develop resistance to ARSIs, resulting in poor clinical outcome. The molecular mechanisms underlying AR-mediated prostate cancer progression remain unclear. In a new study published in Nature Communications, co-corresponding author Egon Ogris and his team, together with collaborators from the University of Pennsylvania, the University of Michigan and the University Medical Center Hamburg-Eppendorf, show that leucine carboxy methyl transferase 1 (LCMT1) suppresses AR signaling and that its product, methylated protein phosphatase 2A (PP2A), is a valuable prognostic marker and potential therapeutic target.