PALD1 (phosphatase domain containing paladin 1) is a putative protein tyrosine phosphatase localized to the cytosol, cytoplasm, and nucleus with protein binding capabilities 1. Primary function involves vascular endothelial cell regulation and lung development. PALD1 is expressed in both epithelial and mesenchymal compartments of the postnatal lung and is required for normal vascular development and lung function in a sex-specific manner 1. Loss of PALD1 in female mice results in increased endothelial cell apoptosis and proliferation, leading to emphysema-like pathology with impaired lung function 1. PALD1 has been implicated in insulin signaling, innate immunity, and neural crest migration 1. Clinically, PALD1 variants are associated with multiple vascular and neurological diseases. Differential methylation of PALD1 was identified in Alzheimer's disease entorhinal cortex tissue and correlates with altered gene expression 2. Rare PALD1 variants segregate with familial moyamoya angiopathy in European families 3, and pathogenic variants associate with subarachnoid hemorrhage risk 4. In aging studies, PALD1 upregulation marks vascular endothelial aging and correlates with endothelial junction instability, though PALD1 knockdown recovers vascular permeability 5. Additionally, PALD1 variants associate with pancreatic cancer susceptibility in first-degree relatives 6 and exhibit female-specific effects on body mass index in admixed populations 7.