CHML (CHM-like) encodes Rep2, a substrate-binding component of the Rab geranylgeranyltransferase complex that facilitates prenylation of Rab proteins essential for vesicle-mediated transport. CHML functions by binding unprenylated Rab proteins and presenting them to the catalytic subunit for geranylgeranyl modification, though it is less effective than CHM in supporting Rab3 family prenylation 1. The protein promotes vesicular trafficking by facilitating Rab protein recycling, particularly Rab14 in liver cancer cells 2 and Rab5A in lung cancer cells 3. CHML expression is elevated in multiple cancers including hepatocellular carcinoma, non-small cell lung cancer, and correlates with poor patient survival and increased metastasis 243. The gene is regulated as an NRF2 target and mechanistically controls mTOR function by mediating its translocation and activation at lysosomes 4. CHML is also targeted by miR-199a-3p, which normally suppresses its oncogenic effects 3. Clinically, CHML represents a potential therapeutic target for cancer treatment, as its dysregulation promotes tumor growth, metastasis, and drug resistance through altered vesicular trafficking pathways.