Here, we characterized two prototypical isoforms of the PMEPA1 gene: PMEPA1-a (coding 287 amino acid, also known as STAG1/TMEPA1) and PMEPA1-b (coding 252 amino acid, also known as PMEPA1) in the context of androgen/TGF-β signaling in prostate cancer cells, and further explored the clinical relevance and biomarker features of PMEPA1 isoforms with prostate cancer late-stage progression by conducting a molecular-epidemiology investigation among prostate cancer patients in a health professional follow-up study. Here, PMEPA1 is linked to prostate cancer.