The ubiquitous Galphas-subunit of the trimeric, stimulatory G-protein plays a central role in receptor-mediated signal transduction, coupling receptor activation with the production of cAMP. The Galphas-encoding locus Gnas is now known to consist of a complex arrangement of several protein-coding and noncoding transcripts. We provide an overview of its genomic organization, its regulation by genomic imprinting, and a summary of the physiological roles of the alternative protein variants Galphas and XLalphas as determined from deficient mouse models.