Given that the Pdk1 knockout mice were previously reported to be lethal [47], to further evaluate the potential role of PDK1 in SPOP functions in vivo, the PDK1 lower expressing mutant Pdk1K465E knock-in [48] or Akt1 knockout mice [49] will be employed to cross with the Spop mutation knock-in mice [27], and provide robust evidence for the pathological roles of the PDK1-AKT pathway for SPOP tumor suppressor function. Here, AKT1 is linked to neoplasm.