This review highlighted and summarizes the isoform specific functions of PMEPA1 gene, stratified PMEPA1 gene family members with expression profiling, responsiveness to androgen and TGF-β as well as cancer biological behavior in context of AR and TGF-β signaling with plausible explanations of dysfunctions of AR and TGF-β signaling in prostate tumorigenesis and aggressive progression. The gene discussed is PMEPA1; the disease is cancer.