Rab escort protein 1 (CHM) (REP1)

Rab escort protein 1 (REP1), encoded by the CHM gene, is a critical component of the Rab geranylgeranyltransferase (GGTase) complex essential for the post-translational modification of Rab GTPases (UniProt P24386). Its primary biological function is to bind newly synthesized Rab proteins and present them to the catalytic subunit of Rab GGTase for prenylation, a lipid modification necessary for membrane anchoring and the regulation of intracellular trafficking (NCBI Gene ID: 1121). In humans, a deficiency in REP1 leads to Choroideremia, a rare X-linked recessive retinal degeneration characterized by the progressive loss of the choroid, retinal pigment epithelium, and photoreceptors (MacLaren et al., 2014). While a closely related isoform, REP2, can compensate for REP1 in most tissues, it is insufficient in the retina, leading to the tissue-specific disease phenotype. Therapeutic strategies for this target focus on gene replacement therapy, utilizing adeno-associated virus (AAV) vectors to deliver a functional copy of the CHM gene to the subretinal space (Dimopoulos et al., 2018). These treatments aim to restore prenylation activity and halt the progression of vision loss in affected patients.

Other names

CHMChoroideremia proteinRab proteins geranylgeranyltransferase component ADXS540TCDGGTA

Gene replacement therapy via adeno-associated virus (AAV) vector delivery of a functional CHM gene to restore Rab escort protein 1 activity and Rab prenylation.