Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a genetic predisposition to sunlight-induced skin cancer; it is commonly due to deficiencies in DNA repair enzymes. The most frequent mutations are found in the XP genes from group A through G and group V, which encode for nucleotide excision repair proteins. XPF, which is also designated ERCC4 or ERCC11, associates directly with the excision repair cross-complementing 1 (ERCC1) factor. ERCC1, a functional homolog of Rad10 in S. cerevisiae, is a component of a structure-specific endonuclease that is responsible for 5' incisions during DNA repair. The ERCC1/XPF endonuclease preferentially cleaves one strand of DNA between duplex and single-stranded regions near borders of the stem-loop structure and, thereby, contributes to the initial steps of the nucleotide excision repair process.