Nicotinic acetylcholine receptors (nAChRs) are pentameric neurotransmitter-gated ion channels which are expressed at the vertebrate neuromuscular junction (muscle-type nAChRs) and within the nervous system (neuronal nAChRs). Nicotinic receptors have been implicated in several neuromuscular and neurological disorders and are increasingly being seen as important targets for therapeutic drug discovery. Nicotinic receptors are also expressed within the invertebrate nervous system and are major targets for insecticides which are used extensively in areas of animal health and crop protection. Nicotinic receptors display considerable heterogeneity in their subunit composition (17 different nAChRs subunits have been identified in vertebrates and about 10 subunits in insect species). As with other multisubunit neurotransmitter receptors, heterologous expression studies have been used extensively to examine the influence of nAChR subunit composition upon the pharmacological and functional diversity of receptor subtypes. However, for several nAChRs subtypes, considerable difficulties have been encountered in efficient functional heterologous expression of recombinant receptors. This has been a particular problem for insect nAChRs and also for several mammalian subtypes such as homomeric α7 nAChRs when expressed in non-neuronal cultured cell lines (1). RIC-3 is a nAChR-associated transmembrane protein, originally identified in C. elegans (2), which is encoded by the gene ric-3 (resistant to inhibitors of cholinesterase). It has also been cloned and characterised from other several other species, including humans. There is evidence that RIC-3 is required for nAChR maturation (2) and it has been shown to enhance levels of functional expression of nAChR subtypes such as α7 when expressed in Xenopus oocytes. More significantly, co-expression of human and C. elegans RIC-3 is able for facilitate functional expression nAChRs such as α7 in otherwise non-permissive cell lines (3-5). We have also found that RIC-3 can enhance levels of functional expression in cultured cell lines of several other nAChR subtypes, including heteromeric nAChRs such as α4β2 (4). In contrast, there have been reports that RIC-3 reduces or abolishes functional expression of some other nAChR subtypes. Recent studies appear to indicate that the effect of RIC-3 upon maturation and functional expression of nAChRs is influenced markedly by the host cell type.