The premature aging and cancer predisposition observed in RJALS patients are caused by mutations of the SPRTN gene, resulting in a C-terminally truncated protein (ΔC, amino acid [aa] 1–246 of SPRTN followed by eight amino acids [X8] caused by a frameshift) or a tyrosine-to-cysteine substitution (Y117C, SPRTN-YC) in close proximity to the active site (Figure 3A) (Lessel et al., 2014). This evidence concerns the gene SPRTN and progeroid features-hepatocellular carcinoma predisposition syndrome.