H2AC6 is a core histone protein that functions as a structural component of nucleosomes, the fundamental units of chr6 organization [UniProt]. As part of the nucleosome complex, H2AC6 wraps DNA and regulates chr6 accessibility, playing central roles in transcription regulation, DNA repair, DNA replication, and chr6 stability [UniProt]. The protein participates in heterochromatin formation and chr6 organization through post-translational modifications and nucleosome remodeling [GO Annotations]. Regarding disease relevance, H2AC6 expression has been identified as a risk factor in intervertebral disc degeneration (IVDD), where elevated H2AC6 expression positively correlates with increased degeneration risk through lactylation-related mechanisms 1. In esophageal squamous cell carcinoma (ESCC), H2AC6 emerged as one of three novel genes critical for patient survival, identified through comparative transcriptomic analysis across global populations 2. Additionally, H2AC6 was among downregulated genes in circulating extracellular vesicles following exercise training in long COVID patients, suggesting involvement in inflammation and metabolic pathways responsive to therapeutic intervention 3. These findings suggest H2AC6 may serve as a biomarker for ESCC prognosis and potentially a therapeutic target in lactylation-related degenerative diseases, though further mechanistic studies are needed to establish causal relationships.