Concerning the wide range of diseases associated with changes in XPF protein due to its crucial role in several DNA repair pathways, the objective of this study was to better understand the role of XPF in DNA repair and human disease by analyzing the genotype-phenotype correlation of XPF/ERCC4 pathogenic variants causing XP, FA, CS, XFE or CS/XP in a genetically homogeneous background. This evidence concerns the gene ERCC4 and xeroderma pigmentosum.