PPP3CC encodes the gamma catalytic subunit of calcineurin, a calcium-dependent, calmodulin-stimulated protein phosphatase essential for intracellular Ca²⁺-mediated signal transduction 1. The enzyme dephosphorylates key transcription factors including NFATC1 (activation) and ELK1 (inactivation), and regulates synaptic plasticity through calcineurin-NFAT signaling cascades 2. PPP3CC is prominently expressed in hippocampal excitatory neurons and plays critical roles in neuronal adaptation and long-term cellular responses 3. Genetic variants in PPP3CC have been associated with bipolar disorder and schizophrenia susceptibility, with decreased hippocampal PPP3CC expression documented in schizophrenia patients 13. Beyond psychiatry, PPP3CC functions as a tumor suppressor: its expression is downregulated in gliomas by ZEB1, leading to constitutive NF-κB activation and enhanced tumor progression 4. In cancer contexts, PPP3CC upregulation via JNK/P38/MAPK pathway activation inhibits NSCLC cell proliferation and migration 5. Additionally, PPP3CC transcription is induced during adaptive stress responses, contributing to neuroplasticity and cognitive resilience in models of Alzheimer's disease and stroke 6. Elevated PPP3CC expression characterizes hyperinflammatory acute respiratory distress syndrome, correlating with enhanced T-cell and interferon signaling 7.