In conclusion, we show for the first time that (i) K6 proteins are incorporated into mature tooth enamel at the rod sheaths, (ii) SNPs in KRT6 genes are associated with increased susceptibility to dental caries, (iii) a PC patient with a mutation in KRT6A exhibits defects in enamel structure, and (iv) caries-associated p.Ser143Asn substitution in K6 proteins impairs proper protein interactions. The gene discussed is KRT6A; the disease is dental caries.