Mucins are critical components of the mucosal barrier that protect against infection. They are secreted by mucosal epithelial cells and form a physical and chemical barrier, along with other antimicrobial molecules, to prevent pathogen entry. Mucins also interact with the innate and adaptive immune systems, and pathogens have evolved strategies to subvert these defenses. Mucosal surfaces are coated with a viscous mucus layer that varies in thickness and is constantly renewed. This layer, along with the glycocalyx on the cell surface, provides a matrix for antimicrobial molecules and helps trap pathogens. Mucins are large glycoproteins with complex carbohydrate structures that can be modified in response to infection, altering their role in host defense. The biosynthesis and structure of mucins are highly variable, with different subfamilies playing distinct roles in the mucosal barrier. Cell-surface mucins are particularly important as they form part of the glycocalyx and can be shed to act as decoys for pathogens. Mucin glycosylation is regulated by genetic and environmental factors, influencing their ability to resist microbial attack. Pathogens can evade the mucin barrier by degrading mucin components, motility through mucus, or invading through specialized cells like M cells. Understanding mucin biology is essential for developing strategies to prevent and treat mucosal infections. Current research highlights the dynamic nature of mucins and their interactions with the immune system, emphasizing the need for further studies to fully understand their role in host defense.Mucins are critical components of the mucosal barrier that protect against infection. They are secreted by mucosal epithelial cells and form a physical and chemical barrier, along with other antimicrobial molecules, to prevent pathogen entry. Mucins also interact with the innate and adaptive immune systems, and pathogens have evolved strategies to subvert these defenses. Mucosal surfaces are coated with a viscous mucus layer that varies in thickness and is constantly renewed. This layer, along with the glycocalyx on the cell surface, provides a matrix for antimicrobial molecules and helps trap pathogens. Mucins are large glycoproteins with complex carbohydrate structures that can be modified in response to infection, altering their role in host defense. The biosynthesis and structure of mucins are highly variable, with different subfamilies playing distinct roles in the mucosal barrier. Cell-surface mucins are particularly important as they form part of the glycocalyx and can be shed to act as decoys for pathogens. Mucin glycosylation is regulated by genetic and environmental factors, influencing their ability to resist microbial attack. Pathogens can evade the mucin barrier by degrading mucin components, motility through mucus, or invading through specialized cells like M cells. Understanding mucin biology is essential for developing strategies to prevent and treat mucosal infections. Current research highlights the dynamic nature of mucins and their interactions with the immune system, emphasizing the need for further studies to fully understand their role in host defense.