Abstract: Aspects of the disclosure relate to compositions and methods for modulating expression of certain RPGR retinitis pigmentosa GTPase regulator (RPGR) proteins in a cell or subject. In some embodiments the disclosure provides expression vectors encoding one or more RPGR proteins and/or one or more inhibitory nucleic acids that target certain isoforms of RPGR, for example RPGRCONST. In some aspects, the disclosure relates to methods of treating retinitis pigmentosa (RP) in a subject by administering compositions that modulate RPGR expression or activity.