PTDSS1

Phosphatidylserine synthase 1 (PTDSS1), also termed PSS1, is a key enzyme encoded by the PTDSS1 gene that catalyzes the biosynthesis of phosphatidylserine (PS) through base-exchange reactions converting phosphatidylcholine or phosphatidyl ethanolamine to PS. This membrane-bound enzyme localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs) and regulates phospholipid homeostasis critical for cellular membrane architecture, vesicular trafficking, and apoptotic signaling. PTDSS1-mediated PS synthesis participates in mTORC1 signaling, coagulation cascades, and immune recognition pathways through PS externalization. Dysregulation of PTDSS1 has been implicated in autosomal recessive Lenz-Majewski hyperostotic dwarfism (caused by gain-of-function mutations) and metabolic disorders like nonalcoholic fatty liver disease. Recent studies suggest its potential involvement in cancer metastasis via PS-dependent immunosuppressive microenvironments. While no direct PTDSS1-targeted therapies exist, pharmacological modulation of PS metabolism through lipid nanoparticle formulations and scramblase inhibitors is being explored for neurodegenerative diseases and cancer immunotherapy.