Intestinal goblet cells and mucins play a critical role in the innate immune defense of the gastrointestinal tract. Goblet cells produce secretory mucins (e.g., MUC2), bioactive molecules (e.g., TFF, RELMβ, Fcgbp), and membrane-bound mucins (e.g., MUC1, MUC3, MUC17). These components form a mucus layer that protects the epithelium from pathogens and maintains intestinal homeostasis. The mucus layer consists of an outer "loose" layer and an inner "adherent" layer, with the outer layer containing mucin oligosaccharides that support microbial colonization, while the inner layer is largely free of bacteria. Defects in mucin production, such as those caused by MUC2 deficiency, lead to increased bacterial adhesion, intestinal permeability, and susceptibility to colitis. Mucin gene expression and glycan structures are altered in intestinal cancers, contributing to tumor progression. Goblet cells are regulated by multiple signaling pathways, including Notch, Wnt/β-catenin, and PI3K/Akt, which influence their differentiation and function. MUC2 is the primary secretory mucin produced by goblet cells and is essential for mucus network formation. MUC2 is highly glycosylated and forms trimers through disulfide bonds, contributing to the viscosity of the mucus layer. MUC3, a membrane-bound mucin, has structural and functional roles in maintaining epithelial integrity. The mucus layer interacts with the intestinal microbiota, with commensal bacteria residing in the outer layer and pathogenic bacteria avoiding the inner layer. Probiotics like Lactobacillus plantarum can enhance mucus production and inhibit pathogen adhesion. In diseases such as cystic fibrosis, mucin dysfunction leads to mucus accumulation and impaired mucosal defense. In inflammatory bowel disease (IBD), mucin defects and dysbiosis contribute to intestinal inflammation. Mucinous adenocarcinoma is characterized by high mucin production and altered glycosylation, which may serve as diagnostic and therapeutic targets. Understanding the regulation of mucin synthesis, glycosylation, and interactions with the microbiota is essential for developing therapies for intestinal diseases. Further research is needed to elucidate the mechanisms underlying mucin changes in cancer and inflammation, as well as the role of mucins in cancer progression and immune responses.Intestinal goblet cells and mucins play a critical role in the innate immune defense of the gastrointestinal tract. Goblet cells produce secretory mucins (e.g., MUC2), bioactive molecules (e.g., TFF, RELMβ, Fcgbp), and membrane-bound mucins (e.g., MUC1, MUC3, MUC17). These components form a mucus layer that protects the epithelium from pathogens and maintains intestinal homeostasis. The mucus layer consists of an outer "loose" layer and an inner "adherent" layer, with the outer layer containing mucin oligosaccharides that support microbial colonization, while the inner layer is largely free of bacteria. Defects in mucin production, such as those caused by MUC2 deficiency, lead to increased bacterial adhesion, intestinal permeability, and susceptibility to colitis. Mucin gene expression and glycan structures are altered in intestinal cancers, contributing to tumor progression. Goblet cells are regulated by multiple signaling pathways, including Notch, Wnt/β-catenin, and PI3K/Akt, which influence their differentiation and function. MUC2 is the primary secretory mucin produced by goblet cells and is essential for mucus network formation. MUC2 is highly glycosylated and forms trimers through disulfide bonds, contributing to the viscosity of the mucus layer. MUC3, a membrane-bound mucin, has structural and functional roles in maintaining epithelial integrity. The mucus layer interacts with the intestinal microbiota, with commensal bacteria residing in the outer layer and pathogenic bacteria avoiding the inner layer. Probiotics like Lactobacillus plantarum can enhance mucus production and inhibit pathogen adhesion. In diseases such as cystic fibrosis, mucin dysfunction leads to mucus accumulation and impaired mucosal defense. In inflammatory bowel disease (IBD), mucin defects and dysbiosis contribute to intestinal inflammation. Mucinous adenocarcinoma is characterized by high mucin production and altered glycosylation, which may serve as diagnostic and therapeutic targets. Understanding the regulation of mucin synthesis, glycosylation, and interactions with the microbiota is essential for developing therapies for intestinal diseases. Further research is needed to elucidate the mechanisms underlying mucin changes in cancer and inflammation, as well as the role of mucins in cancer progression and immune responses.