We have greatly advanced our understanding of how glycans decorating the surface of human cells, protect and maintain the homeostasis of our epithelial tissues, such as skin. By tweaking the genetic blueprints of tissue models to turn off specific genes responsible for creating these sugars, we have uncovered exiting insights into the wide range of roles these molecules play. For example, our experiments show that certain glycan structures are essential for the skin to form properly and act as a barrier, while other glycans are essential for how cells migrate, and heal wounds. The glycans also help cells stick together and communicate with each other, which is vital for the healthy function of our epithelial tissues. This work, which involved cutting-edge techniques like CRISPR-Cas9 gene editing and 3D tissue models, highlights just how complex and crucial these sugar structures are. They are not just decorative, but key players in vital biological processes. Our findings, open new doors for exploring how cells communicate and how this knowledge can be applied, for example, to better understand diseases like cancer. Additionally, we have developed new methods to map out the sugar structures on cell surfaces, significantly advancing our ability to study how these molecules vary under both healthy and pathological conditions. In the context of viral infections, our findings have illuminated how glycans affcet viral infections. By examining skin cells genetically engineered to lack certain sugars, we've learned how different sugars can impact the stages of herpes virus infection. This not only adds a new layer to our understanding of viral infections but also showcases the power of genetic engineering in dissecting the complex interactions between viruses and their host cells. In summary, our research have found that cell surface glycans are far from simple decorations, but instead play fundamental roles in health, disease, and host-pathogen interactions.