PROM2 (prominin 2) is a transmembrane glycoprotein localized to the plasma membrane, cell projections, and membrane microdomains 1. While its primary molecular function remains incompletely characterized, PROM2 plays critical roles in cellular processes including endocytosis regulation, GTPase activity modulation, and membrane organization based on GO annotations. Mechanistically, PROM2 functions through multiple signaling pathways. It associates with multivesicular bodies (MVBs) and regulates ferroptosis sensitivity via CRM1-mediated nuclear export 2. PROM2 also activates the PI3K/AKT signaling axis, and its expression is regulated by p53-dependent pathways and transcriptional control by HOXC11 31. Clinically, PROM2 overexpression is a significant biomarker for poor prognosis across multiple cancer types 45. In melanoma, renal cell carcinoma, and triple-negative breast cancer, elevated PROM2 promotes epithelial-to-mesenchymal transition (EMT) and confers ferroptosis resistance, driving metastatic potential 6. In cardiac pathology, PROM2 represents a novel marker of cardiomyocyte senescence, correlating with hypertrophy and heart failure with preserved ejection fraction 1. Additionally, PROM2 is associated with a ciliopathy-related COPD endotype 7. Therapeutically, PROM2 inhibition synergizes with ferroptosis-inducing agents like artesunate and RSL3 to suppress tumor growth, positioning PROM2 as a promising therapeutic target across multiple malignancies.