With a Vdr-knockout mouse model and CRISPR/Cas9 gene editing, as well as the technical advances in gene/mRNA/16S ribosomal sequencing, we should be able to address these questions and obtain definitive evidence to determine whether vitamin D is effective for the prevention or/and treatment of PC and to develop mechanism-based, effective therapeutic strategies to improve the outcomes of PC. The gene discussed is VDR; the disease is pachyonychia congenita.