Overall, these findings of a previously unanticipated association between reduced WFS1 and CRYM protein expression and HIV/SIV-induced neuroimmune activation provide novel insights into the pathogenesis of HAND and the translational value of cannabinoids in attenuating HIV/SIV-mediated neuroimmune activation, ER and oxidative stress. This evidence concerns the gene CRYM and HIV-associated neurocognitive disorder.