Nineteen different OPRM1 spliced variants have been described in humans (Pasternak 2004, 2014; Xu et al. 2014a; Lu et al. 2015). OPRM1 alternative splicing may also influence susceptibility to HIV-1 infection (Dever et al. 2012, 2014). Although many variants are thought to be non-functional and fail to traffic from the endoplasmic reticulum, increasing evidence suggests they may oligomerize other G Protein-coupled receptors or bind chaperones to assist in trafficking to the plasma membrane (Samoshkin et al. 2015; Zhu et al. 2019). Quantitative and qualitative differences in human MOR splice variant expression levels have been noted across different CNS cell types following exposure to HIV (Dever et al. 2012, 2014). Interestingly, an excitatory, MOR-1 K splice variant, that couples to GαS (Gris et al. 2010) is preferentially expressed in human astroglia (Dever et al. 2012) and has been shown to correlate with HIVE and cognitive impairment (Dever et al. 2012, 2014).