Histone lysine methyltransferases (HKMT) are a class of enzymes responsible for site-specific methylation of lysine residues. Histone methylation has an essential role in Plasmodium falciparum virulence gene expression and developmental stage development including sexual commitment (gametocytes). Histone methylation marks can be responsible in either transcriptional gene activation or silencing depending on the residue. We have shown recently that drugs that target histone methylation such as BIX-01294 block malaria parasite development. In P. falciparum the HKMT family consists of 10 predicted proteins (named PfSET1 to 10) all carrying a SET-domain which is essential for its methyltransferase activity, of these 6 are essential for the parasite during the asexual blood stage. We have successfully expressed and characterized the full length PfSET7 methyltransferase, which is essential for parasite growth. PfSET7 is an AdoMet-dependent histone 3 lysine methyltransferase with highest activity towards lysines 4 and 9. It localizes to distinct cytoplasmic foci in both blood stage and liver stage parasites. Enzymatic characterization of this essential enzyme now allows us to screen small molecule compound libraries to identify inhibitors. Hits will then be phenotypically screened on cultured parasites. The final goal is to explore HKMT inhibitors for development of new anti-malarias.