Key factors contributing to NEPC have been identified, particularly mutations in FOXA1 and SPOP found in primary prostate cancer (PCa), lineage plasticity resulting from RB1 loss and TP53 dysfunction, as well as the activation of the polycomb repressive complex 2 (PRC2), including components such as EZH2, in advanced PCa cases (10). Here, SPOP is linked to posterior cortical atrophy.