We report here 2 cases of adult HSE in patients with very rare variants in mannan-binding lectin serine protease 2 (MASP-2), the gene encoding a protease considered as the central activator of the lectin pathway of the complement system (the most ancient, besides the classical and alternate pathways of complement activation), because of its ability to form complexes with several pattern recognition molecules including mannose-binding lectin (MBL), collectins (CL-L1 and CL-K1) and ficolins (FCN1, FCN2 and FCN3 also called M-, L- and H-ficolin respectively). The gene discussed is MBL2; the disease is herpes simplex encephalitis.