Herein we proved a robust evidence in support of in vivo interaction between GATA2 and SMAD4 and thus sought to unravel the mechanistic roles of TGFβ1/SMAD4 in the GATA2-dependent context in PCa tumor progression to advanced stages and to understand how GATA2 and SMAD4 mediate inherited PCa risk. Here, SMAD4 is linked to posterior cortical atrophy.