CGRRF1 (cell growth regulator with ring finger domain 1) is a RING-finger-containing ubiquitin E3 ligase that negatively regulates cell growth and proliferation. CGRRF1 functions in endoplasmic reticulum-associated degradation (ERAD) and is upregulated by ER stress 1. In cancer biology, CGRRF1 acts as a ubiquitin E3 ligase targeting KRAS for proteasomal degradation, thereby suppressing the KRAS/ERK pathway 2. CGRRF1 also regulates Wnt signaling by mediating ERAD-dependent ubiquitination of the Wnt cargo receptor Evi, controlling Wnt protein secretion 3. In endometrial cancer, CGRRF1 expression is significantly reduced compared to normal tissue, and its overexpression inhibits cancer cell proliferation, suggesting loss of CGRRF1 promotes tumorigenesis 4. CGRRF1 is induced by metformin treatment in obesity-associated endometrial pathology, making it a potential biomarker for therapeutic response 4. CGRRF1 is also dysregulated in rheumatoid arthritis and shows elevated expression in RA patients, suggesting involvement in autoimmune pathogenesis 5. Additionally, CGRRF1 variants are associated with age-related macular degeneration 6 and are epigenetically deregulated in testicular germ cell tumors 7. These findings position CGRRF1 as a multifunctional tumor suppressor and disease-relevant regulator of protein degradation pathways.