Mechanistically, LoX may affect GBM biology through multiple processes: (1) haploinsufficiency of X-linked tumor suppressors such as KDM6A, ATRX, or FOXP3, which regulate chromatin, DNA repair, and immune evasion; (2) loss of biallelic expression of escapee genes involved in immune signaling or proliferation (e.g., TLR7, CD40LG, KDM5C); (3) unmasking of recessive alleles on the remaining X chromosome; and (4) altered immune activation due to loss of X-linked immunoregulatory loci. Here, CD40LG is linked to glioblastoma.