PTDSS1 Recombinant Rabbit mAb (S-5055-48)

PTDSS1 (phosphatidylserine synthase 1, PSS1) is a multi-pass transmembrane enzyme encoded by the PTDSS1 gene on human chromosome 8 that localizes to the endoplasmic reticulum membrane, particularly to mitochondria-associated membranes (MAMs), and catalyzes a calcium-dependent base-exchange reaction in which serine is substituted for phosphatidylcholine (PC, the principal substrate) or phosphatidylethanolamine (PE) as the donor, thereby generating phosphatidylserine (PS). The enzyme's activity is subject to feedback inhibition by exogenous PS, thereby maintaining phospholipid homeostasis. Gain-of-function mutations in PTDSS1 (such as p.Arg95Gln and p.Pro269Leu) reduce its sensitivity to PS feedback inhibition, leading to increased PS synthesis and causing the rare autosomal dominant disorder Lenz–Majewski syndrome (LMS), which manifests as cutis laxa, progressive osteosclerosis, craniofacial and dental abnormalities, intellectual disability, and distal limb anomalies. Mechanistic studies have further shown that mutant PSS1 can reduce PI4P levels at the Golgi apparatus and plasma membrane by activating the Sac1 phosphatase, interfering with lipid metabolism at ER–PM and ER–Golgi contact sites. In addition, PTDSS1 has attracted attention in tumor biology: its loss can reduce specific PS levels in tumor cells and affect tumor-associated macrophage infiltration, while selective PTDSS1 inhibitors can induce collateral lethality in cancers with PTDSS2 deficiency.