C1GALT1C1 encodes Cosmc, an X-linked molecular chaperone that is essential for proper O-glycosylation of glycoproteins. Cosmc specifically assists the folding and stability of core 1 β-3-galactosyltransferase (C1GALT1/T-synthase), which synthesizes the universal T-antigen (Galβ1-3GalNAcα1-Ser/Thr) precursor for extended O-glycans 1. Loss of Cosmc function leads to accumulation of pathological Tn-antigen (GalNAcα1-Ser/Thr) on multiple glycoproteins instead of normal O-glycan structures 1. Mutations in C1GALT1C1 cause a novel congenital disorder of glycosylation (COSMC-CDG) characterized by developmental delay, immunodeficiency, thrombocytopenia, and atypical hemolytic uremic syndrome (aHUS) 12. The aHUS phenotype results from exposed T-antigen on erythrocyte surfaces triggering complement-mediated thrombotic microangiopathy 2. Patients respond to complement inhibitor therapy with Eculizumab 1. C1GALT1C1 deficiency also causes Tn polyagglutination syndrome 3 and affects IgA1 galactosylation in IgA nephropathy 4. Recent studies demonstrate that C1GALT1C1 expression can be regulated by metabolites like N-acetylspermidine, highlighting its role in maintaining intestinal homeostasis 5. Both germline and mosaic mutations have been described, with females showing variable phenotypes due to X-inactivation patterns 6.