The handful of studies that have been done (1–3; Kawanishi et al., 1998) have not identified any genetic defects causally related to neuroleptic malignant syndrome, but there are many other, as yet untested, candidates. Most notable among these, in my opinion, are the regulatory proteins that maintain intracellular electrochemical homeostasis through their function as calcium buffers and channels. Multiple individual point mutations affecting genetic loci for several of these proteins are known to cause malignant hyperthermia. Considering the many clinical features shared by neuroleptic malignant syndrome and malignant hyperthermia, it seems reasonable to hypothesize that similar but distinct mutations affecting this heterogenous group of proteins could be the basis for vulnerability to developing neuroleptic malignant syndrome. In this model, the role of sympathoadrenal hyperactivity would be analogous to that of volatile anesthetics in malignant hyperthermia—i.e., hyperstimulated adrenoceptors interact with a genetically defective regulatory protein to produce excessive intracellular calcium levels.