PLCH2 encodes phospholipase C eta 2, a calcium-sensitive enzyme that mediates production of second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) through phosphatidylinositol-specific phospholipase C activity 1. The enzyme plays important roles in neuronal development and calcium mobilization within the brain, particularly in processes including axon growth, synapse formation, and neurotransmitter responses 2. PLCH2 is expressed postnatally in the brain and may be critical for neuronal network formation and maintenance 2. Disease relevance includes associations with neurodevelopmental disorders; PLCH2 is a candidate gene for mental retardation in patients with 1p36 deletions 2, and rare compound heterozygous loss-of-function variants have been identified in bladder exstrophy cases 3. Additionally, PLCH2 methylation has been identified as a mediator in multiple pathophysiological contexts: mediating selenium exposure effects on blood lipid metabolism 4, serving as a prognostic biomarker in colorectal cancer pyroptosis-related pathways 5, functioning as a biomarker in abdominal aortic aneurysm with expression primarily in T cells 6, and mediating male age effects on reproductive outcomes through sperm methylation changes 7. PLCH2 also represents a candidate disease gene from exome sequencing studies in Saudi Arabian populations with Mendelian phenotypes 8.