It is well established that Speckle-type POZ protein (SPOP) is among the most commonly mutated tumor suppressor genes in human primary PCa, and its mutations can result in dysregulated proteasome degradation of many proteins such as AR, ERG and BRD4, thus driving prostate tumorigenesis, aberrant AR transcriptional activity, genomic instability and also therapy-resistance (58). This evidence concerns the gene ERG and posterior cortical atrophy.