This is a lethal subtype of prostate cancer characterized by the expression of neuroendocrine (NE) markers such as chromogranin A (CHGA), synaptophysin (SYP), enolase 2 (ENO2) and CD56, together with the loss of androgen receptor (AR) signaling, thereby resulting in resistance to AR-targeted therapy, tumor aggressiveness and poor clinical outcome [29] (Figure 2). Here, SYP is linked to Familial prostate cancer.