By searching sequence databases for homologs of Dictyostelium discoideum Impas, which shares homology with presenilin, followed by PCR of lymphocyte and hippocampus cDNA libraries, Grigorenko et al. (2002) cloned SPPL2a. This protein, which may act as an intramembrane protease, contains an N-terminal protease-associated (PA) domain, several transmembrane regions, a hydrophilic loop, conservative sequences around the first and second aspartate residues, and an invariant PAL motif near the C terminus.