CD44 is a multifunctional cell surface transmembrane glycoprotein that serves as a key mediator of cellular adhesion, migration, and signaling pathways 1. The protein functions primarily as a receptor for extracellular matrix components, particularly hyaluronic acid (HA), osteopontin, and matrix metalloproteinases, driving numerous cancer-associated signaling cascades 1. CD44 undergoes alternative splicing to produce standard (CD44s) and variant (CD44v) isoforms that interact with different ligands to regulate cellular processes 1. The protein plays critical roles in autophagy regulation, where its intracellular domain (CD44ICD) negatively controls autophagy by reducing PIK3R4 and PIK3C3 levels and disrupting STAT3-dependent complexes, linking autophagy decline to vascular aging 2. In cancer biology, CD44 functions as a cancer stem cell marker, promoting self-renewal, epithelial-mesenchymal transition, and resistance to therapy 1. The protein is stabilized through deubiquitination by USP10, enhancing breast cancer cell proliferation, stemness, and metastasis via activation of PDGFRβ/STAT3 signaling 3. Additionally, CD44 mediates inflammatory responses by facilitating neutrophil extracellular trap formation and Th17 cell differentiation through a feedback loop involving IL-17A 4. Beyond cancer, CD44 has emerging roles in metabolic regulation, particularly in insulin resistance associated with obesity and diabetes 5.