RNF6 (ring finger protein 6) is a RING-type E3 ubiquitin ligase located on chromosome 13.2 1 that functions as a dual-function protein with both ubiquitin ligase and transcriptional regulatory activities. As an E3 ligase, RNF6 mediates K48-linked polyubiquitination of multiple substrate proteins including p27, cyclin D2, and LIMK1, targeting them for proteasomal degradation 23. RNF6 also functions as a transcriptional regulator, binding DNA promoters to activate expression of target genes such as SF3B2 and SKP2 42. These dual mechanisms converge on cell cycle regulation and proliferation control through pathways including Akt/mTOR, Wnt/β-catenin, and JAK2/STAT3 signaling 56. Notably, RNF6's role in cancer is context-dependent: it functions as an oncogene in colorectal cancer, glioblastoma, and retinoblastoma, promoting proliferation and drug resistance 427, but exhibits tumor-suppressive activity in lung adenocarcinoma 3. Somatic mutations in RNF6 have been identified in esophageal squamous cell carcinoma, suggesting involvement in this malignancy 8. RNF6 represents a promising therapeutic target, with inhibitors showing effectiveness in suppressing tumor growth 6.