Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions

The protein kinase C (PKC) family represents pivotal regulators in cellular signaling, whose dysregulation has been implicated in diverse human diseases, including cancer, neurodegenerative disorders, and metabolic syndromes. PKCs transduce extracellular signals through lipid-mediated activation and controlled subcellular translocation. Their activity is orchestrated by a multistep life cycle, encompassing constitutive phosphorylation during maturation, second messenger-dependent activation, and agonist-driven termination. Despite extensive investigation, critical gaps remain in the isoform-specific signaling networks and the structural determinants that underlie PKC functional diversity, thereby limiting the development of targeted therapies. In this review, we provide a comprehensive analysis of the PKC family, covering isoform diversity, structural and functional attributes, physiological roles, involvement in disease pathogenesis, therapeutic targeting strategies, as well as current controversies and research challenges. PKCs precisely regulate cell fate through subtype-specific signaling networks, and their structural plasticity presents unique opportunities for therapeutic intervention. By integrating recent advances from structural biology, disease models, and clinical trials, this review proposes a unified framework of PKC regulation that bridges fundamental biology with translational innovation. Ultimately, it serves as a valuable resource for elucidating the multifaceted roles of PKCs in health and disease, while providing a conceptual basis for the rational design of next-generation therapeutics.