The intestinal epithelial cell-surface molecule, CD98 is a type II membrane glycoprotein. Molecular orientation studies have demonstrated that the C-terminal tail of human CD98 (hCD98), which contains a PDZ-binding domain, is extracellular. In intestinal epithelial cells, CD98 is covalently linked to an amino-acid transporter with which it forms a heterodimer. This heterodimer associates with beta(1)-integrin and intercellular adhesion molecular 1 (ICAM-1) to form a macromolecular complex in the basolateral membranes of polarized intestinal epithelial cells. This review focuses on the multifunctional roles of CD98, including involvement in extracellular signaling, adhesion/polarity, and amino-acid transporter expression in intestinal epithelia. A role for CD98 in intestinal inflammation, such as Intestinal Bowel Disease (IBD), is also proposed.