Susceptibility to herpes simplex virus type 1 (HSV-1) encephalitis (HSE-1) in otherwise healthy individuals, in the course of primary infection, can be caused by single-gene inborn errors of Toll-like receptor 3 (TLR3) dependent, interferon (IFN)-α/β-mediated immunity,^1,2 or by single-gene inborn errors of snoRNA31.³ These variations underlie infections of the forebrain, whereas mutations of DBR1 underlie infections of the brainstem.³ HSV-2 encephalitis (HSE-2) is typically observed in neonates, albeit also rarely in older children and adults.⁴ Its manifestations include altered level of consciousness, cranial neuropathies or more extensive brainstem encephalitis, hemiparesis, hemisensory loss, and permanent neurologic deficit.⁴ MRI in HSE-2 may show normal findings, nonspecific white matter, orbitofrontal, mesial temporal lobe, or brainstem lesions. Inborn errors of immunity underlying HSE-2 have not been described.