Phosphatidylserine synthase 1 (PSS1)

Phosphatidylserine synthase 1 (PSS1) is a membrane-bound enzyme mainly localized in the endoplasmic reticulum, where it catalyzes the base-exchange reaction that forms phosphatidylserine (PS) from phosphatidylcholine (PC) (and to a lesser extent from phosphatidylethanolamine)[1][2][3][7]. This enzyme plays a major role in producing PS, a key acidic phospholipid critical to cell membrane structure, particularly in neurons and other tissues[6][7]. PS is enriched on the inner leaflet of the plasma membrane and is involved in cell signaling, apoptosis, and membrane trafficking[5][6][7]. Mutations in the PTDSS1 gene are causative for Lenz-Majewski hyperostotic dwarfism, underscoring the enzyme's importance in normal human development[2]. PSS1 regulation is complex, involving feedback inhibition by PS and transcriptional control by factors such as Sp1, Sp3, and N-Myc, especially in the brain[4][7]. While there are currently no direct, clinically approved drugs targeting PSS1, pharmacologic modulation of its expression or activity is of research interest due to its central role in phospholipid metabolism and disease[4].

Other names

PTDSS1PS synthase 1Phosphatidylserine synthetase 1

Inhibition or modulation decreases phosphatidylserine biosynthesis, impacting membrane composition and downstream signaling. Drug effect via transcriptional regulation of PTDSS1 (e.g., mithramycin disrupts Sp-family transcription factor binding[4]). Indirect targeting may sensitize cells to apoptosis or affect cell proliferation by altering membrane lipid composition.