The Profilaggrin N-terminal(proFLG-N) consists of two distinct domains, an S100-like A-domain and B domain. After proFLG-N transfection at a growing phase of NHK, only proFLG-N expressing cells exhibited DNA degradation. Therefore, A-domain in proFLG-N is responsible for DNA degradation. These results indicate that proFLG-N play an important role in the keratinocyte terminal differentiation, especially in the denucleation process. On the other hand, we identified novel S100 fused-type proteins, filaggrin-2(FLG2) and trichohyalin-like protein 1(TCHHL1). The structural features and expression profile of FLG2 were similar to those of profilaggrin. The deduced amino acid sequence of TCHHL1 contains one trans-membrane domain. The TCHHL1 protein was expressed in the basal layer.