CHML (gene)

CHML, also known as CHM-like or Rab escort protein 2 (REP2), is a human gene that encodes for a protein involved in prenylation of Rab GTPases. Rab GTPases are crucial for intracellular vesicle trafficking, and their proper function relies on prenylation, a post-translational modification involving the attachment of lipid moieties.

The CHML protein acts as a chaperone, specifically a Rab escort protein (REP), guiding newly synthesized Rab proteins to the cell membrane and presenting them to a geranylgeranyl transferase (GGTase) enzyme for prenylation. Without proper prenylation, Rab proteins cannot effectively anchor to the cell membrane and thus cannot participate in vesicular transport.

CHML is highly homologous to another Rab escort protein, CHM (REP1), which is implicated in X-linked choroideremia. While mutations in CHM cause choroideremia, a progressive degeneration of the choroid, retina, and retinal pigment epithelium, mutations in CHML are less frequently associated with disease. The functional redundancy between CHM and CHML likely explains this difference. However, research suggests that CHML may play a more significant role in specific tissues or cellular processes.

The CHML gene is located on chromosome 1. Its protein product contains several domains, including a highly conserved REP domain responsible for interacting with Rab proteins.

Further research is ongoing to fully elucidate the specific roles and regulatory mechanisms of CHML in various cellular contexts and its potential involvement in disease pathogenesis beyond choroideremia.