Using cell-surface biotinylation followed by mass spectrometry (MS), we revealed substantial differences between the surface proteomes of WT and MGAT1 KO HeLa cells. Among the most strongly depleted proteins in MGAT1 KO cells were those involved in cell adhesion and extracellular interactions, membrane domain organization, and cytoskeletal organization. These include LGALS3 (galectin-3) that cross-links complex N-glycans thus stabilizes these glycoproteins at the surface27; ITGA4, ITGA7 (integrin- α4 and α7), matrix adhesion receptors that also contribute to raft stabilization through their clustering and scaffolding; ICAM1, MCAM, and BCAM that mediate cell-cell and cell-matrix interactions; and CAVIN1, the caveolae-associated scaffolding protein that is essential, together with LGALS3, for caveolae biogenesis. These observations suggest that MGAT1 loss broadly compromises the integrity of host cell membrane microdomain.