PKCη

PKCη is a novel PKC isoform with predominant epithelial expression and a documented role in cell-cycle control, epithelial junction biology, and immune regulation^[1]. Mechanistically, PKCη supports epithelial tight junction integrity by phosphorylating occludin at T403/T404, a finding directly relevant to Caco-2 and MDCK epithelial monolayer models^[2]. In keratinocytes, PKCη associates with the cyclin E/CDK2/p21 complex, phosphorylates p21, inhibits CDK2 activity, and promotes G1 arrest^[3]. In stress and cancer-cell models, PKCη promotes senescence induced by oxidative stress and DNA damage through p21^Cip1^, p27^Kip1^, IL-6, and IL-6 receptor upregulation, while suppressing IL-8^[4]. Compared with related isoforms, PKCη shows isoform-specific biology because different PKCs can exert opposing effects in senescence, and PKCη, rather than PKCθ, controls CTLA-4-mediated regulatory T-cell suppressive function^[4][5]. For experimental applications, PKCη studies should prioritize isoform-selective genetic perturbation, phospho-occludin readouts, senescence markers, and CTLA-4-dependent Treg functional assays^[2][4][5].