RCE1 (Ras converting CAAX endopeptidase 1) is an integral membrane endoprotease localized to the endoplasmic reticulum that catalyzes proteolytic removal of the C-terminal three amino acids from prenylated CaaX proteins 1. The enzyme recognizes prenylated substrates through a glutamate-activated water mechanism and requires specific identity of the a2 amino residue, preferring Ile, Leu, or Val 1. Key substrates include Ras family GTPases, heterotrimeric G-protein gamma subunits, nuclear lamins, and protein kinases 1. RCE1 exists as multiple isoforms, with both isoform 1 and the N-terminally truncated isoform 2 required for proper H-Ras plasma membrane localization; USP17 regulates isoform 2 abundance through deubiquitination 2. Clinically, RCE1 exhibits tissue-dependent roles in cancer. In hepatocellular carcinoma and colorectal carcinoma, reduced RCE1 expression promotes epithelial-mesenchymal transition via P38/TGF-β signaling, enhancing invasion and metastasis, and independently predicts poor prognosis 345. Conversely, prostate cancer shows elevated RCE1 correlating with poor outcomes 6. RCE1 inhibition by anti-HIV protease inhibitors (ritonavir, lopinavir) impairs Rab protein processing, causing Golgi stress and hepatotoxicity 7. These findings establish RCE1 as both a potential therapeutic target and prognostic biomarker across multiple malignancies.