Either loss-of-function mutations of SPOP or gain-of- function mutations of PDK1 in their binding region all attenuate SPOP recognizing and ubiquitinating PDK1, leading to elevated PDK1 protein abundance, AKT kinase activity, and benefit of tumor malignancies, indicating that the PDK1-AKT pathway will be a potential target for mutated SPOP- or PDK1-driven PCa. Here, PDK1 is linked to posterior cortical atrophy.