Conclusion The work presented here has clarified two important questions regarding the physiological roles of the two ubiquitous calpain isoforms, μ- and m-calpain. Firstly, it was determined that m-calpain plays an indispensable role in murine embryogenesis, possibly related to pre-implantation development. Furthermore, this function cannot be carried out by μ-calpain despite the apparent in vitro similarities of μ- and m-calpain, demonstrating that the two isoforms clearly have some distinct roles in vivo. The functions of m-calpain during post-implantation embryogenesis and in adult mice remain to be elucidated and will have to be addressed using a conditional gene targeting strategy.