Lu/BCAM has been recognized as unique receptor for laminin 5 chain in human red blood cells and as co-receptor in epithelial, endothelial and smooth muscle cells. Since limited information is available regarding the function of this adhesion glycoprotein in vivo, we generated Lu/BCAM-null mice and looked for abnormalities in erythroid cells as well as in kidney and intestine, two tissues showing alteration in laminin 5 chain deficient mice. We first showed that in contrast to human, wild type murine red cells failed to express Lu/BCAM. Lu/BCAM-null mice were healthy and developed normally. However, while no alteration of the renal function was evidenced, up to 90 % of the glomeruli from mutant kidneys exhibited abnormalities characterized by a reduced number of visible capillary lumens and irregular thickening of the glomerular basement membrane. Similarly, intestine analysis of mutant mice revealed smooth muscle coat thickening and disorganization. Since glomerular basement membrane and smooth muscle coat express laminin 5 chain and are in contact with cell types expressing Lu/BCAM in wild type mice, these results provide evidence that Lu/BCAM, as a laminin 521 receptor, is involved in vivo in the maintenance of normal basement membrane organization in the kidney and intestine.