The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparinn are indispensable for parasite survival since merozoite surface proteins-1, -2, -4, -5, and -10, crucial for erythrocyte invasion, are GPI-anchored. Therefore, the GPI biosynthetic pathway can offer potential targets for novel anti-malarial drugs. Here, we characterized the putative P. falciparum PIG-B gene (PfPIGB) that encodes mannosyltransferase-III of GPI biosynthesis. PfPIGB mRNA is transcribed in a developmental stage specific manner. A protein corresponding to the expected size of PfPIG-B is expressed by the parasite and is localized in the endoplasmic reticulum. Treatment of parasites with PfPIG-B specific siRNA caused reduction in GPI synthesis, affecting the PIG-B specific GPI intermediate. These data demonstrate that PfPIG-B is functional and encodes mannosyltransferase-Ill of the parasite GPI biosynthesis. The parasite PfPIG-B is novel in that its signature sequence HKEHKI is unique and is only partially conserved as compared to HKEXRF signature motif of mammalian PIG-B enzymes. (C) 2007 Elsevier Inc. All rights reserved.