Novel human protein H4, mutation leads to familial neuroborreliosis with meningitis, aseptic meningitis and facial nerve palsy. We describe a previously uncharacterized mutation in H4 that encodes a human ribosomal protein S4. We have named this gene 'RP-H4' after the gene symbol RPS4. It was discovered in patients with familial neuroborreliosis who had associated meningitis, aseptic meningitis and facial nerve palsy. The clinical features of familial neuroborreliosis and the neurological complications of borreliosis are reviewed. RPS4 is the fourth component of the small ribosomal subunit. These cases illustrate that this protein plays an important role in ribosomal assembly and translation of a group of eukaryotic mRNAs in the central nervous system. This is the first case of a human disease due to mutation in an r-protein. We have previously suggested that human ribosomal proteins could be a target for development of selective agents in antimicrobial chemotherapy and/or development of anticancer agents. The implications of this finding are discussed.