CA8 (carbonic anhydrase 8) is an enzymatically inactive member of the carbonic anhydrase family that functions as a critical allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) in neuronal calcium signaling 1. Unlike other carbonic anhydrases, CA8 lacks catalytic activity but plays essential roles in regulating intracellular calcium homeostasis by inhibiting ITPR1-mediated calcium release from the endoplasmic reticulum 1. The protein acts as a binding partner for ITPR1, particularly in cerebellar neurons, where this interaction is crucial for proper neuronal function 2. CA8 also modulates neuronal excitability by activating Kv7 voltage-gated potassium channels, which prolongs afterhyperpolarization and reduces somatosensory neuronal excitability 3. Biallelic mutations in CA8 cause autosomal recessive cerebellar ataxia (spinocerebellar ataxia type 34), characterized by progressive cerebellar atrophy, neurodevelopmental disorders, and variable motor symptoms including ataxia, pyramidal signs, and dystonia 4. The gene is located on chromosome 8-q12 and is regulated by Sp1 transcription factor through GC-box elements in its promoter 56. Therapeutic applications include gene therapy approaches for chr8 pain management, where CA8 overexpression provides prolonged analgesia through modulation of calcium signaling and potassium channel activation 7.