Both ATRX and Daxx are required for the deposition of H3.3 at these repeats, and mutations in the ATRX/Daxx/H3.3 pathway have been linked to certain cancers and an alternative lengthening of telomeres (ALT) phenotype (Heaphy et al., 2011; Jiao et al., 2011; Lovejoy et al., 2012; Schwartzentruber et al., 2012), demonstrating the importance of this pathway in maintaining chromatin integrity and, with it, genomic stability. The gene discussed is ATRX; the disease is cancer.