One area of E. histolytica biology that has been understudied is how the parasite recognizes and responds to its environment. Although signaling in E. histolytica through G-proteins and mitogen-activated protein kinases has been described [4,5], the genome project has delineated an entirely new repertoire of potential signal-transduction pathways [2,6]. All of the major families contained within the eukaryotic protein kinase superfamily are represented within the E. histolytica genome, including tyrosine kinases with Src homology (SH)2 domains, tyrosine-kinase-like protein kinases and putative receptor serine/threonine kinases. The serine/threonine receptor kinases fall into three families, two of which are characterized by extracellular domains with CXXC or CXC repeats [2,6]. Interestingly, CXXC repeats are found in the highly abundant variant surface antigens of the intestinal protozoan Giardia lamblia, where they have been linked to the conferral of parasite resistance to host intestinal proteases . More than 100 protein phosphatases were identified in the E. histolytica genome; among them was a small family of genes encoding proteins in which a serine/threonine phosphatase domain is linked to a region containing leucine-rich repeat motifs. These motifs mediate primarily protein–protein interactions and, although some proteins with leucine-rich repeats are known to contain kinase domains, leucine-rich repeat proteins with phosphatase activity have been described only recently [8,9]. There is extensive diversity in the leucine-rich repeats, with at least seven subfamilies identified . The leucine-rich repeats linked to the E. histolytica phosphatases are primarily of the ‘typical’ or ‘classic’ subtype but the genome also contains a large gene family (>100 members) that encodes proteins with leucine-rich repeats of the Treponema pallidum subtype (TpLRR), similar to those seen in the BspA surface protein of the bacteria Bacteroides forsythus [9,10]. The BspA protein has been implicated in the binding of B. forsythus to host extracellular-matrix proteins, suggesting a potential function for the newly discovered E. histolytica BspA-like proteins.