GPCPD1 (glycerophosphocholine phosphodiesterase 1) is a ubiquitous enzyme that catalyzes the hydrolysis of glycerophosphocholine (GPC) to choline, with roles extending far beyond its enzymatic function. 1 Primary Function and Mechanism: GPCPD1 functions as a key regulator of glycerophospholipid metabolism, particularly in choline homeostasis. 2 Under hypoxic conditions, GPCPD1 undergoes depalmitoylation and relocates to the outer mitochondrial membrane, where it binds VDAC1 to regulate its oligomerization state, thereby promoting PRKN-mediated mitophagy. 3 The enzyme is expressed across multiple tissues including skeletal muscle, intestinal epithelium, and brain. 1 Disease Relevance: GPCPD1 dysregulation associates with multiple pathologies. Muscle-specific GPCPD1 deficiency causes severe glucose intolerance and 'aged-like' transcriptomic signatures, with impaired insulin signaling. 2 The GPCPD1-GPC pathway is perturbed in aging and type 2 diabetes patients. 2 GPCPD1-mediated mitophagy promotes triple-negative breast cancer growth and metastasis. 3 Reduced GPCPD1 expression occurs in Huntington's disease striatum and cortex, contributing to choline metabolism dysregulation. 4 Clinical Significance: GPCPD1 represents a potential diagnostic biomarker for acute myocardial infarction 5 and prognostic indicator in triple-negative breast cancer. 3 Restoring GPCPD1 function through metabolic modulation shows therapeutic promise for metabolic and neurodegenerative diseases.