SHISA7 (shisa family member 7) is a transmembrane auxiliary protein that plays crucial roles in regulating both GABAergic and glutamatergic neurotransmission in the brain. As a GABAA receptor (GABAAR) auxiliary subunit, SHISA7 modulates receptor trafficking to synapses, accelerates channel deactivation kinetics, and potently enhances benzodiazepine action 1. At the single-channel level, SHISA7 reduces GABAAR opening frequency and decreases burst duration and open probability, providing a mechanistic basis for its effects on deactivation 2. SHISA7 is particularly important for regulating tonic inhibition mediated by extrasynaptic α5-GABAARs, with this regulation being activity-dependent and requiring protein kinase A phosphorylation 3. Beyond GABAergic function, SHISA7 belongs to the CKAMP family of AMPA receptor auxiliary proteins, potentially influencing glutamatergic transmission 4. Disease relevance includes associations with Alzheimer's disease, where SHISA7 expression is reduced in patient brain tissue and peripheral blood 5, and opioid use disorder, where SHISA7 expression correlates with heroin-seeking behavior and is identified as a potential therapeutic target 6. The protein's regulation of both inhibitory and excitatory transmission positions it as a key modulator of synaptic plasticity and neural circuit function.