3. Conclusions and perspectives
Because of the absence of research tools for in vivo evaluation, studies on PLD2 function have been conducted primarily at the molecular and cellular level. Recently, genetically engineered mouse models have been developed, and they have given researchers the opportunity to validate proposed functions and identify novel roles of PLD2 at the organismal level. In contrast to previous expectations, however, PLD2 KO mice have not shown an evident phenotype under normal conditions. Molecular compensation by either other isoform(s) or PA-generating enzymes, or systemic compensation at the organismal level, could be possible explanation for this phenomenon. Much effort has gone into unveiling PLD2 functions in particular conditions such as diseases, allowing better prediction of its functions than normal conditions. Recent reports have suggested specific contributions of PLD2 to pathological conditions, such as pathological angiogenesis, sepsis, and Alzheimer's disease. However, many pathophysiological conditions, including cancer development, remain to be tested. In addition, because PLD2 is expressed ubiquitously in most cell types, more intricate studies using conditional KO (tissue-specific and inducible) animal models are required to clearly reveal the cell-, tissue-, and organ-specific functions of PLD2. Recent studies have shown ameliorating effects of isotype-specific inhibitors of PLD on some diseases. The new inhibitors overcame limitations of previously used pan-PLD inhibitors. Furthermore, the use of an effective PLD2 inhibitor will provide opportunities to better understand PLD2 functions in various disease conditions and suggest potential therapeutic strategy for these diseases.
