PRKCZ (protein kinase C zeta) is a serine-threonine kinase involved in multiple physiological and pathological processes. Functionally, PRKCZ participates in late-phase synaptic long-term potentiation and long-term memory maintenance in hippocampal CA1 cells, with roles in cell polarity establishment and intracellular signal transduction [GO Annotations]. The kinase regulates both positive and negative aspects of insulin receptor signaling and promotes ERK1/2 cascade activation through protein phosphorylation [GO Annotations]. Mechanistically, PRKCZ is induced in cancer cells co-cultured with M2-polarized macrophages and is required for macrophage-mediated radioresistance in inflammatory breast cancer, with inhibition of PRKCZ reducing this resistance 1. In HPV-related head and neck squamous cell carcinoma, PRKCZ hypermethylation suppresses invasion and epithelial-mesenchymal transition via Cdc42 signaling, suggesting dual roles depending on methylation status 2. UTR genetic variants in PRKCZ alter mRNA structure, stability, and transcription factor/miRNA binding sites, influencing gene expression 3. Clinically, PRKCZ variants show association with multiple diseases: bipolar disorder through chromosome 1 linkage 4, type 2 diabetes in Han populations 5, active ulcerative colitis in genome-wide Mendelian randomization studies 6, and acute coronary syndrome with causal evidence from epigenome-wide association studies 7. These findings establish PRKCZ as a potential therapeutic target across cardiovascular, neurological, oncological, and metabolic disorders.