LY75 (lymphocyte antigen 75) is a mannose receptor and endocytic receptor primarily expressed on dendritic cells, functioning in receptor-mediated endocytosis and immune regulation 1. Beyond its established role in antigen processing and presentation, LY75 exhibits pleiotropic functions in cancer biology and hematologic disease. In ovarian cancer, LY75 overexpression promotes mesenchymal-to-epithelial transition and metastatic potential, with opposite effects in epithelial cancer cells, suggesting context-dependent regulation of cellular phenotype 1. LY75 is highly expressed in bladder cancer, where its downregulation by nitidine chloride inhibits proliferation, migration, invasion, and induces apoptosis 2. LY75 functions as a host restriction factor for viral entry by suppressing furin-dependent proteolytic processing of SARS-CoV-2 spike protein 3. Genomically, LY75 variants are associated with reduced clonal hematopoiesis of indeterminate potential incidence 4, platelet traits 5, and identified as a causal gene for myeloid leukemia risk 6. LY75 promoter methylation independently predicts poor melanoma outcome, including recurrence and metastasis development 7. These findings indicate LY75 functions as a pleiotropic modulator of immune response, cancer progression, and hematologic disease susceptibility, with potential therapeutic targeting implications.