LYPD8 is a secreted, glycosylated protein that functions as a critical component of intestinal mucosal barrier defense. Primary function: LYPD8 prevents invasion of gram-negative flagellated bacteria into the colonic epithelium by binding to bacterial flagella and inhibiting their motility, thereby maintaining segregation of commensal microbiota from the inner mucus layer 1. Mechanism: The protein operates through glycan-dependent binding to flagellated bacteria such as Proteus mirabilis and inhibits attachment of pathogenic bacteria like Citrobacter rodentium by binding to intimin and blocking epithelial interaction 23. Disease relevance: LYPD8 expression is significantly reduced in inflammatory bowel disease patients and colorectal cancer tissues, particularly advanced stages 4. Loss of LYPD8 results in spontaneous colitis under dysbiosis conditions and increased susceptibility to DSS-induced colitis 51. In colorectal cancer cells, LYPD8 overexpression inhibits proliferation and migration by reducing IL-6 and TNF-α secretion through suppression of STAT3 and P65 phosphorylation 4. Clinical significance: Recombinant human LYPD8 protein supplementation shows therapeutic potential for inflammatory bowel disease, ameliorating both chemical and diet-induced colitis in preclinical models 5.