Xeroderma Pigmentosum (XP) is an autosomal recessive disorder characterized by a genetic predisposition to sunlight-induced skin cancer, and 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, is a 115 kDa protein that associates directly with the excision repair cross-complementing 1 (ERCC1) factor. ERCC-1, 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 singlestranded regions near borders of the stem-loop structure and, thereby, contributes to the initial steps of the nucleotide excision repair process.