PRKCI encodes protein kinase C iota (PKCι), an atypical serine/threonine kinase that functions as a calcium- and diacylglycerol-independent regulator of cell survival and polarity. The protein plays a central role in protecting cells against apoptotic stimuli through multiple mechanisms: it blocks pro-apoptotic factors like BAD in glioblastoma cells, prevents amyloid-beta-induced neuronal apoptosis, and is necessary for BCR-ABL-mediated drug resistance in leukemia. PKCι also coordinates epithelial cell polarity by phosphorylating EZR and organizing the apical domain, and regulates microtubule dynamics in the secretory pathway. In cancer contexts, PKCι functions as an oncogenic driver across multiple tumor types. In colorectal cancer, Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis 1 and phosphorylates Tgfbr1 to stabilize TGF-β signaling, enhancing epithelial-to-mesenchymal transition and metastasis 2. In pancreatic cancer, PRKCI cooperates with RIPK2 to enhance NF-κB, JNK, and ERK phosphorylation, promoting growth and metastasis 3. The circular RNA form of PRKCI (circ-PRKCI) functions as an oncogenic driver in papillary thyroid cancer and hepatocellular carcinoma through competing endogenous RNA mechanisms 4. High PRKCI expression independently predicts poor overall survival in gastric cancer 5. Clinically, PKCι is targeted by kinase inhibitors including midostaurin, sotrastaurin, and UCN-01. Additionally, recent evidence reveals that loss-of-function PRKCI variants cause Van der Woude syndrome and syndromic orofacial clefts through disruption of periderm development 6, establishing the gene's role in developmental epithelial biology distinct from its cancer-associated functions.