PTPN1 (protein tyrosine phosphatase non-receptor type 1) is a non-receptor tyrosine phosphatase that regulates insulin and leptin signaling pathways, functioning as a negative regulator of metabolic homeostasis 1. Its primary mechanism involves dephosphorylation of the insulin receptor and suppression of downstream PI3K/AKT signaling 1, and it also mediates dephosphorylation of PERK to regulate endoplasmic reticulum unfolded protein response [UniProt]. Additionally, PTPN1 controls cell migration by localizing to ER-PM contact sites at the cell rear, where it dephosphorylates receptor tyrosine kinases to confine signaling to the cell front 2. In obesity-associated type 2 diabetes, adrenomedullin-mediated PTPN1 activation in endothelial cells promotes insulin receptor dephosphorylation, contributing to systemic insulin resistance 3. PTPN1 inhibition emerges as a therapeutic strategy: the inhibitor K884 enhances STAT3 phosphorylation and promotes myogenic differentiation in Duchenne muscular dystrophy muscle stem cells 4, while the compound farrerol alleviates hepatic insulin resistance and steatosis in metabolic-associated fatty liver disease through PTPN1 inhibition 1. In neuroblastoma, elevated PTPN1 expression associates with metastasis and poor prognosis 5. Genetic studies show PTPN1 variants display modest associations with type 2 diabetes and obesity susceptibility 6, though findings remain inconsistent across populations 7.