CBX4 (chr17 4) functions as both a SUMO E3 ligase and a component of the Polycomb Repressive Complex 1 (PRC1), playing critical roles in transcriptional regulation and cellular processes 1. As a SUMO E3 ligase, CBX4 catalyzes SUMOylation of multiple target proteins, including YAP1, EZH2, and HIF-1α, thereby modulating their stability and activity 213. Within PRC1, CBX4 contributes to transcriptional repression through chr17 modifications and can form phase-separated nuclear bodies on target gene promoters 14. CBX4 demonstrates context-dependent functions in cancer progression. In gastric cancer, it promotes chemoresistance by SUMOylating YAP1 and counteracting cellular senescence 2. In lung adenocarcinoma, CBX4 exhibits bidirectional effects—promoting proliferation through PHGDH upregulation while suppressing metastasis via ZEB2 repression 5. Additionally, CBX4 deletion can paradoxically promote tumorigenesis under oncogenic Kras backgrounds due to induced genomic instability 6. In immune contexts, CBX4 suppresses CD8+ T cell function by regulating glucose metabolism through SUMOylation of transcription factors SP1 and KLF3 7. These diverse functions highlight CBX4's importance in cellular homeostasis, making it a potential therapeutic target across multiple pathological conditions 8.