PLCH1 (phospholipase C eta 1) is a calcium-activated phosphatidylinositol-specific phospholipase C enzyme that mediates the production of second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), functioning in phosphatidylinositol-mediated signaling pathways [UniProt]. The protein localizes to the cytoplasm and plasma membrane, participating in phosphatidylinositol-4,5-bisphosphate hydrolysis and calcium ion release [GO annotations]. PLCH1 plays a critical role in embryonic forebrain development. Homozygous deleterious variants in PLCH1 cause holoprosencephaly spectrum disorders, including congenital hydrocephalus, alobar holoprosencephaly, and cyclopia, with PLCH1 expression observed in notochord, developing spinal cord, and cerebellum—tissues producing or responding to sonic hedgehog signaling 1. Pathogenic variants can cause cytoplasmic-to-nuclear mislocalisation, disrupting normal protein function 1. In cancer biology, PLCH1 overexpression correlates with poor prognosis. In breast cancer, elevated PLCH1 correlates with hormone receptor and HER2 expression, promoting cell proliferation through the ERK1/2-EGR1 signaling axis 2. A PLCH1 genetic variant (rs181696) associates with increased squamous cell carcinoma risk in Chinese nonsmokers 3. Additionally, PLCH1 upregulation contributes to cytokine-induced imatinib resistance in chr3 myeloid leukemia via an SRSF1/PRKCH/PLCH1 axis 4. These findings establish PLCH1 as a developmental regulator and cancer-associated gene with therapeutic targeting potential.