H2BC1 encodes testis-specific histone 2B (TSH2B), a variant histone that replaces somatic H2B during spermiogenesis to facilitate histone-to-protamine transition in male germ cells 1. As a core nucleosome component, TSH2B regulates chr6 dynamics by promoting nucleosome dissociation, enabling large-scale histone exchange necessary for proper genome condensation 1. In infertile men, reduced TSH2B and total H2B levels are significantly associated with oligozoospermia and oligoasthenozoospermia, indicating defective histone replacement 1. Notably, TSH2B phosphorylation correlates with sperm motility, as asthenozoospermic men show normal TSH2B levels but significantly reduced phosphorylated TSH2B 1. H2BC1 expression is regulated by 5' UTR genetic variants (rs4711096, rs4712959) and promoter methylation; the rs4711096 minor allele frequency is significantly lower in infertile men 12. H2BC1 abundance varies with paternal age, being upregulated in young adults but downregulated in advanced age groups 3. As a diagnostic marker, H2BC1 and related proteins show discriminatory potential for distinguishing azoospermia subtypes 4. These findings establish H2BC1 as essential for male fertility through chr6 compaction and sperm motility regulation.