PDE6D has been first recognized as a chaperone for the catalytic PDE6A and PDE6B subunits (1). Prenylated PDE6A and PDE6B had been found to be bound by PDE6D to be solubilized from membranes possibly as regulatory function in the visual cascade (10), (10).
PDE6D interacts with RPGR in a thermosensitive fashion. Interaction is abolished by mutations in the RCC1-domain of RPGR (12).
Latest results indicate a function on small GTP-binding proteins by stabilizing the GTP-bound state (11).

For transfer of geranylgeranyl modifications to Rab proteins two Rab escort proteins (REP1 and REP2) are required. These escort proteins act as substrate carriers for Rab-Geranyl-Geranyl-transferase (GGTase II) which catalyses the attachment of geranylgeranyl modifications from geranylgeranyl-diphosphate (GG-PP) to the Rab-protein.
REP1 and REP2 are coexpressed throughout the body. Due to substrate specificities of REP1 for Rab3A, and Rab3D, Rab proteins abundant to neural-tissues, deficiencies in REP1 lead to phenotypes affecting retinal tissues. Further studies revealed a further REP1 specific Rab protein termed Rab27a due to its size of 27 kDa. Rab27a is slightly bigger than the usual size of Rab proteins. Substrate specificities of Rab27A, Rab3A and Rab3D result in considerably lowered affinity of REP2 to these REP1 specific substrates(4), (17).. Rab27a is selectively unprenylated in CHM patients (19) indicating an involvement in the pathogenesis of CHM. In contrast mutations in Rab27A do not cause CHM or other retina associated disturbances. This is supported by studies on transgenic mice expressing dominant-negative Rab27a mutations causing slowed preferential GDP-binding, reduced GTPase-activity, and inhibition of GTP/GDP exchange. In these studies mice did not show any signs in the retina but expressed extensive cataracts and corneal and stromal ring opacities. (14)
Human Rab27a mutations cause Griscelli syndrome a rare autosomal recessive disorder expressing pigmentary dilution of the skin and hair, large clumps of pigment in hair shafts and accumulation of melanosomes in melanocytes (13). This indicates an involvement of Rab27A in the intracellular routing of melanosomes.
The relationship of Rab GGTase, Rab proteins, and REP summarises as follows:
The REP-Rab complex attaches to the catalytic dimer of Rab GGTase which transfers a geranylgeranyl group from GG-PP to the Rab protein. Geranylated-Rab stays attached to REP and is escorted to the Rab-specific protein target (4).
The target proteins are currently unknown. Investigations on REP1 deficient mice showed a possible effect on embryonic membranes which causes Rep1 null mutations to be lethal in mice (20).