SERPINF1 encodes pigment epithelium-derived factor (PEDF), a neurotrophic and anti-angiogenic protein that lacks conventional serine protease inhibitor activity despite its serpin classification. In normal physiology, SERPINF1 promotes neuronal differentiation and regulates bone homeostasis through mechanisms involving protein secretion and extracellular localization. Pathologically, SERPINF1 dysregulation is associated with multiple diseases. Biallelic SERPINF1 mutations cause osteogenesis imperfecta type VI, an autosomal recessive disorder where mutant PEDF proteins misfold and accumulate in the endoplasmic reticulum of osteoblasts, triggering ER stress, apoptosis, and impaired mineralization 1. ER-associated degradation and autophagy partially mitigate this cellular toxicity 1. Heterozygous mutation carriers exhibit reduced serum PEDF but normal bone density and lipid profiles 2. In glioma, elevated SERPINF1 expression correlates with poor prognosis (hazard ratio 1.7-4.1) and promotes tumor stemness, proliferation, and invasion through Notch signaling activation 3. SERPINF1 variants and reduced expression also associate with otosclerosis, an otic capsule bone disorder, with down-regulation observed in affected stapes tissue 45, though one large study questioned this association 6. Clinically, SERPINF1 status represents a prognostic marker in glioma and a disease-causing gene in rare genetic bone disorders.