The cationic and amphipathic properties of hdefensins, like a-defensins, have been reported to be important for antimicrobial activities by disrupting microbial membrane structures. Through systematic phylogenetic analyses, a detailed classification and nomenclature of the primate a-/h-defensins was provided. The classification of simian a-/hdefensins based on phylogenetic trees is Notoginsenoside-R1 related to their expression patterns in myeloid and enteric tissues. Further phylogenetic classification of simian a-defensins into six functional gene clusters corresponds to their functional divergence. In a previous study, this multigene family was classified into three classes based on neighbor-joining and maximum parsimony trees using genes from simians sequences as well as one mouse adefensin sequence as Saikosaponin-B2 the outgroup. However, there is no explanation of how hNek6 activates this pathway and the first possible links to that question were addressed by our yeast two-hybrid results that showed hNek6 interactions with Transcription factor RelB, Prx-III and TRIP-4. The first neighbors expansion of our network was not able to show enrichment in I-kappaB kinase/NFkappaB cascade, but in apoptotic process and transcription, where these proteins were found as most enriched. Therefore, our hypothesis is that hNek6 may interact directly with any of those two-hybrid interactors, possibly regulating them by phosphorylation, which could regulate their interaction with Beta-arrestin-1 and/or Estrogen receptor, finally inhibiting these proteins and activating the pathway.