Despite the expression of multiple Rho GDP/GTP exchange factors (GEFs) in the nervous system, the Kalrn gene, which encodes multiple isoforms of Kalirin, plays an essential, non-redundant role. Linkage analyses identified Kalrn as a major risk factor for coronary artery disease and stroke [1-3], as well as for schizophrenia and adult attention-deficit/hyperactivity disorder [4-6]. In addition, Kalirin interacts with many different proteins including deleted in schizophrenia 1 (DISC1), a major risk factor for schizophrenia, the inducible form of nitric oxide synthase (iNOS; NOS2), Huntingtin-associated protein 1 (HAP1) and peptidylglycine α-amidating monooxygenase, an essential enzyme for neuropeptide biosynthesis [7-11]. Chronic cocaine treatment increases levels of Kal7 protein in the mouse and rat striatum [12]. Estrogen treatment of ovariectomized female rats increases Kalirin expression [13], and Alzheimer's Disease is accompanied by a dramatic loss of Kal7 in the hippocampus [14]. Hippocampal Kalirin mRNA is elevated at 4 h following a kainate-induced seizure and remains elevated for a month [15].
