BAG2 (Bcl2-associated athanogene 2) functions as a co-chaperone and nucleotide-exchange factor for HSP70/HSC70, promoting ADP release and client protein recycling 1. Beyond classical chaperone functions, BAG2 acts as a metabolite sensor detecting arginine availability; upon arginine deficiency, it releases SAMD4B to stabilize ATF4 and promote cancer cell survival 2. BAG2 forms stress-induced phase-separated condensates that route clients to the 20S proteasome via ubiquitin-independent degradation mechanisms, particularly during hyper-osmotic stress 3. Disease relevance is substantial. In cervical cancer, BAG2 inhibits STING ubiquitination and stabilizes it, activating type I interferon signaling to suppress progression; low BAG2 correlates with poor prognosis 4. Conversely, BAG2 promotes hepatocellular carcinoma and malignant pleural mesothelioma progression through distinct mechanisms—activating P38/MAPK signaling and serving as a cancer-driver gene, respectively [PMID:36718954; 57]. In liposarcoma, high BAG2 expression predicts worse outcomes 6. BAG2 exhibits neuroprotective functions in neurodegenerative diseases, contrasting its tumor-promoting roles in most cancers 7. These context-dependent functions suggest BAG2 as a potential therapeutic target, with inhibitors warranted in malignancies but agonists in neurodegeneration.