TMEM108 is a transmembrane protein required for proper cognitive function and glutamatergic neurotransmission in the dentate gyrus 1. The protein is enriched in postsynaptic density fractions and is essential for AMPA receptor surface expression and normal excitatory postsynaptic currents in dentate gyrus granule neurons 1. TMEM108 also regulates dendritic spine formation and maturation; deficiency results in fewer and smaller spines 1. Beyond synaptic function, TMEM108 participates in BDNF-dependent signaling pathways and regulates microtubule organization and retrograde axonal transport through interaction with dynein/dynactin motor complexes. Genetic variants in TMEM108 have been associated with multiple neuropsychiatric and neurological conditions. The gene was identified as a novel schizophrenia susceptibility locus with mutations causing cognitive impairment and sensorimotor gating deficits 1. TMEM108 variants also show genome-wide significant association with bipolar disorder risk in Han Chinese populations 2, suggestive associations with cognitive progression in Parkinson's disease 3, and potential association with ischemic stroke 4. Additionally, TMEM108 variants are associated with differential interferon signaling in cancer immunity 5 and show inverse associations with prostate cancer risk 6. These findings establish TMEM108 as a multifunctional protein critical for synaptic function with broader implications for neuropsychiatric and neurological disease pathogenesis.