TCN2 encodes transcobalamin 2 (TC), the primary vitamin B12-binding and transport protein essential for delivering cobalamin to cells 1. TC binds cobalamin with high affinity through specific amino acid residues and facilitates cellular uptake via receptor-mediated endocytosis, with the binding interaction structurally conserved across variants 2. TCN2 deficiency causes severe early-onset disease presenting in infancy with failure to thrive, pancytopenia, hypogammaglobulinemia, and neurological manifestations despite normal circulating B12 levels, reflecting impaired cellular cobalamin delivery 1. Beyond classical deficiency, emerging evidence suggests TCN2 variants contribute to complex diseases: a missense mutation (p.K77M) associated with diabetic nephropathy induces mitochondrial dysfunction and renal tubular damage 3, while TCN2 was identified as a novel susceptibility locus for Alzheimer's disease in Chinese populations 4. Interestingly, TCN2 exhibits unexpected antiviral properties, with upregulation following respiratory syncytial virus infection and demonstrated capacity to inhibit viral replication, suggesting roles beyond canonical B12 transport 5. TCN2 polymorphisms show population-specific effects on B12 metabolism and hematological parameters 6, though associations with nonsyndromic cleft palate remain inconsistent across ethnic groups 78. These findings indicate TCN2 functions extend beyond vitamin B12 transport to encompass immune regulation, metabolic homeostasis, and cellular stress responses.