Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). Interacts with PKN2 (PubMed:15123640). Interacts with TIAM1 and TIAM2 (By similarity). Interacts with HA, as well as other glycosaminoglycans, collagen, laminin, and fibronectin via its N-terminal segment (PubMed:14992719, PubMed:17085435, PubMed:25195884). Interacts with UNC119 (PubMed:19381274). Interacts with PDPN (via extracellular domain); this interaction is required for PDPN-mediated directional migration and regulation of lamellipodia extension/stabilization during cell spreading and migration (PubMed:20962267). Interacts with RDX, EZR and MSN (By similarity). Interacts with EGFR (PubMed:18757307, PubMed:23589287). Interacts with CD74; this complex is essential for the MIF-induced signaling cascade that results in B cell survival (By similarity). Colocalizes with actin in membrane protrusions at wounding edges. Co-localizes with RDX, EZR and MSN in microvilli. Localizes to cholesterol-rich membrane-bound lipid raft domains. Additional isoforms seem to exist. Additional isoforms are produced by alternative splicing of 10 out of 19 exons within the extracellular domain. Additional diversity is generated through the utilization of internal splice donor and acceptor sites within 2 of the exons. A variation in the cytoplasmic domain was shown to result from the alternative splicing of 2 exons. Isoform CD44 is expected to be expressed in normal cells. Splice variants have been found in many tumor cell lines. Exons 5, 6, 7, 8, 9, 10, 11, 13, 14 and 19 are alternatively spliced. Experimental confirmation may be lacking for some isoforms. Isoform 10 (epithelial isoform) is expressed by cells of epithelium and highly expressed by carcinomas. Expression is repressed in neuroblastoma cells. Expressed in the developing retina between 16 and 19 weeks post-conception, specifically in the outer neuroblastic zone, inner neuroblastic zone, interphotoreceptor zone and the retinal pigment epithelium (at protein level). The lectin-like LINK domain is responsible for hyaluronan binding. Proteolytically cleaved in the extracellular matrix by specific proteinases (possibly MMPs) in several cell lines and tumors. N-glycosylated. O-glycosylated. O-glycosylation contains more-or-less-sulfated chondroitin sulfate glycans, whose number may affect the accessibility of specific proteinases to their cleavage site(s). It is uncertain if O-glycosylation occurs on Thr-637 or Thr-638. Phosphorylated; activation of PKC results in the dephosphorylation of Ser-706 (constitutive phosphorylation site), and the phosphorylation of Ser-672. CD44 is responsible for the Indian blood group system. The molecular basis of the In(A)=In1/In(B)=In2 blood group antigens is a single variation in position 46; In(B), the most frequent allele, has Arg-46. Corresponds to the largest isoform. Alternative splice donor/acceptor on exon 5. Lacks exon 6. Alternative splice donor/acceptor on exon 7. Lacks exon 10. Lacks exon 13. Lacks exon 14. Lacks exon 19. Lacks exons 6-11. Lacks exons 6-13. Lacks exons 6-14. Lacks exons 6-11 and exon 14. Lacks exons 6-11, exon 13 and exon 14. Lacks exons 6-14 and exon 19. Alternative splice donor/acceptor on exon 5 and lacks exon 10. Alternative splice donor/acceptor on exon 7 and lacks exon 10. Soluble isoform, has enhanced hyaluronan binding. Blood group antigen gene mutation database CD44 entry