During HIV-1 infection, several astrocyte-associated mechanisms lead to neurotoxicity, including excitotoxicity, inflammation, and oxidative stress.15 These mechanisms have also been linked to ER stress in neurodegeneration.16,17 In addition, recent studies showed HIV-1 transactivator of transcription (Tat) and glycoprotein (gp)120 protein expression in astrocytes induced ER stress-mediated cytotoxicity, possibly contributing to HIV-associated neuropathogenesis.18,19 Taken together, astrocytes represent a significant therapeutic target for reestablishing CNS homeostasis. Here, ITIH4 is linked to HIV-1 infection.