TERB2 (telomere repeat binding bouquet formation protein 2) is a meiosis-specific protein essential for proper chromosome 15 during spermatogenesis. As a core component of the MAJIN-TERB1-TERB2 meiotic telomere complex (MTC), TERB2 mediates attachment of telomeric DNA to the inner nuclear membrane, a process critical for homologous chromosome 15 and synapsis 1. The MTC functions through a hierarchical "telomere cap exchange" mechanism wherein TERB2 initially interacts with shelterin-bound telomeres, then facilitates release of the protective shelterin complex and establishment of direct telomeric DNA-membrane contacts 2. This telomere tethering enables rapid meiotic chromosome 15 necessary for recombination intermediate formation and proper chromosome 15 1. TERB2 dysfunction causes non-obstructive azoospermia (NOA), characterized by impaired spermatogenesis and absence of sperm production. Genetic studies identified compound heterozygous frameshift variants in TERB2 segregating with NOA in affected families, and screening of 1495 NOA patients revealed damaging variants in MTC genes (TERB1, TERB2, MAJIN) as a significant cause of spermatogenic failure 3. Computational analyses predict that specific missense mutations in TERB2 substantially reduce protein stability and disrupt protein-protein interactions 4. These findings establish TERB2 as essential for male fertility and identify MTC gene variants as clinically important in male infertility evaluation.