PRKCG encodes protein kinase C gamma (PKCγ), a calcium- and diacylglycerol-dependent serine/threonine kinase with predominant roles in neuronal signaling and synaptic plasticity. PKCγ phosphorylates key glutamate receptors including GRIA4/GluR4 and GRIN1/NMDAR1, modulating their membrane localization and function in synaptic transmission and long-term potentiation 1. The enzyme also regulates opioid receptor signaling in the spinal cord and limbic system, contributing to morphine-induced effects and nociceptive processing related to pain sensitivity and tolerance 2. PKCγ phosphorylates connexin-43 gap junctions in response to oxidative stress, providing cellular protection 3. Additionally, PKCγ stabilizes the circadian clock component BMAL1 and regulates circadian phase-resetting during temporally restricted feeding 3. Mutations in PRKCG cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar dysfunction 4. SCA14-associated missense mutations result in PKCγ protein instability, aggregation propensity, impaired phosphorylation, mitochondrial dysfunction, and increased apoptosis 5. PRKCG was identified as one of the most common causative genes in hereditary ataxia screening 1. Beyond neurological disease, genetic variants in PRKCG associate with osteosarcoma susceptibility and metastatic progression in Chinese populations 6, and rare PKC fusion events involving PRKCG occur in melanocytic neoplasms 7. PRKCG polymorphisms also show modest association with behavioral disinhibition phenotypes including ADHD 2.