CD44 antigen; Receptor for hyaluronan-mediated motility (RHAMM) (CD44; RHAMM)

CD44 is a broadly expressed cell surface glycoprotein that primarily functions as a receptor for hyaluronan (HA), mediating cell–cell and cell–matrix interactions critical for processes such as cell adhesion, migration, and signaling in homeostasis, inflammation, and cancer. Alternative splicing produces numerous isoforms with varying tissue and disease specificity. RHAMM (CD168) is a non-integral cell surface and intracellular HA receptor that also binds to microtubules and participates in cytoskeletal organization, mitosis, and cell motility. Both CD44 and RHAMM function as key coordinators of cell migration and signaling in tumorigenesis, wound healing, and inflammatory diseases. They frequently interact with each other and other signaling receptors (e.g., PDGFR, ERK/MAPK), and contribute to cancer progression by supporting proliferation, metastasis, and EMT. Therapeutic targeting of the HA-CD44/RHAMM axis is an active area of oncology and fibrosis research, although safety and compensatory mechanisms present significant challenges.

Other names

Homing cell adhesion moleculeHermes antigenLymphocyte-homing receptorCD168HMMR (Hyaluronan-mediated motility receptor)Hyaluronan receptor

Blocking HA (hyaluronan) binding to CD44 or RHAMM inhibits downstream signaling pathways including ERK/MAPK and PI3K/AKT, reducing cell proliferation and migration. Inhibition of CD44 or RHAMM can impair tumor growth, wound healing, and inflammatory responses.