REP1

Rab escort protein 1 (REP-1) is a cytosolic chaperone that binds Rab family GTPases and presents them to the Rab geranylgeranyltransferase complex for prenylation. Prenylation attaches lipid groups that promote Rab association with membranes, enabling vesicular trafficking. REP-1 is encoded by the CHM gene in humans and is broadly expressed, with particularly high levels in retinal pigment epithelium and photoreceptors.

In the cell, REP-1 forms a complex with Rab proteins and Rab geranylgeranyltransferase, facilitating the post-translational modification required for Rab proteins to dock on membranes and regulate vesicle formation, transport, and fusion. A paralog, REP-2, encoded by CHML, can partially substitute REP-1 in some tissues, but not sufficiently in the retina.

Pathogenic mutations in CHM result in loss of REP-1 function and cause X-linked choroideremia, an inherited retinal degenerative disease. Affected individuals experience progressive vision loss due to degeneration of the retinal pigment epithelium, photoreceptors, and choroid; female carriers may show milder symptoms due to skewed X-inactivation.

Research into REP-1 includes animal and cellular models to study Rab trafficking defects and approaches to restore REP-1 activity, including gene therapy to deliver functional CHM. These efforts aim to preserve or restore vision in affected individuals.