STIP1 (stress-induced phosphoprotein 1) functions as a co-chaperone that facilitates HSP90AA1 activity and mediates the association between HSPA8/HSC70 and HSP90 molecular chaperones 1. Through its chaperone-associated selective autophagy (CASA) role, STIP1 participates in protein quality control pathways relevant to neurodegenerative diseases, where it cooperates with autophagy-related components like HSPB8 and BAG3 to promote clearance of misfolded proteins 2. STIP1 also serves as an E3 ubiquitin ligase complex component, regulating protein stability through ubiquitination-mediated degradation; for instance, it mediates YTHDF2 ubiquitination in hepatocellular carcinoma 3 and SHMT2 degradation in lung adenocarcinoma 4. Additionally, STIP1 acts as a transcriptional target of Xbp1s in the unfolded protein response pathway, regulating FoxO1 stability in cardiomyocytes to control metabolic homeostasis 5. Clinically, elevated STIP1 expression correlates with poor prognosis across multiple cancer types, predicting shorter overall survival, earlier lymph node metastasis, and advanced clinical stage 6. Conversely, reduced STIP1 expression shows protective associations in major depressive disorder related to oxidative stress 7. STIP1 also functions in viral pathogenesis by mediating proteasomal degradation of chikungunya virus E1 protein 8.