Trodusquemine and its synthetic analogs represent unique orally available and brain penetrant allosteric inhibitors of PTP1B, and these aminosterols hold promise to be first-in-class drugs that may relieve the burden of such important diseases including type 2 diabetes mellitus, obesity, cancer, neurodegenerative, cardiovascular, and psychiatric disorders (Figure 14). Here, PTPN1 is linked to diabetes mellitus.