Involvement of EFhd2 in membrane and cytoskeleton associated pathways. EFhd2 can associate with detergent resistant membranes (DRM) thought to represent membrane rafts in some B cell lines. Membrane raft association of EFhd2 was also detected in nervous tissue of mice that express a gain of function mutant (G93A) of SOD1. EFhd2 has been shown to exhibit NF-κB-activating as well as NF-κB-inactivating functions in different cell types. Through regulation of NF-κB, EFhd2 may regulate survival or apoptosis of diverse cell types. The interactions of EFhd2 with the SH3 domains of Lyn, PLCγ and Fgr are based on GST-Pull down experiments using recombinant SH3 domains (see Ref. 14). The interactions of Fgr and Lyn SH3 domains with EFhd2 depend on phosphorylation and the SH3 domain of Fgr binds to the predicted proline-rich (PR) SH3 domain binding region of EFhd2. Three phosphorylation sites of EFhd2 are known: S74, S76 and Y83. S74 is a cyclin dependent kinase 1 (Cdk1) site. The ability of EFhd2 to bind calcium may regulate its function and its association with the cytoskeleton. EFhd2 also interacts with hyperphosphorylated Tau in a FTDP17 mouse model as well as in FTDP17 and Alzheimer's patients.