The WT SHP-1 lysate was purified via a 1 ml HisPur™ Ni-NTA column. Cleared lysate was applied to the column resin, followed by a wash step with 10 column volumes of equilibration buffer and 10 column volumes of wash buffer, consisting of 25 mM Tris pH 8.0, 1 mM DTT, 200 mM NaCl, and 20 mM imidazole. Elution for WT SHP-1 was processed using 15 mL elution buffer containing 25 mM Tris pH 8.0, 1 mM DTT, 200 mM NaCl, and 500 mM imidazole. Eluted fractions were tested with pNPP for phosphatase activity. Fractions that showed activity were pooled and dialyzed in 2L equilibration buffer with 0.5 mg TEV protease overnight at 4 °C with gentle stirring. Dialyzed and untagged SHP-1 was applied to a second Ni-NTA column, followed by 10 column volumes of equilibration buffer and 10 column volumes of wash buffer. The flowthrough containing untagged SHP-1 was pooled and concentrated to <12 mL, loaded onto a preequilibrated HiLoad 26/60 Superdex 200 prepgrade column (GE), and purified with 25 mM Tris pH 8.0, 150 mM NaCl, 0.5 mM TCEP. Fractions were assayed with pNPP for activity and purity on a 15% SDS-PAGE gel. Pure protein was concentrated to 10-20 mg/mL, diluted with 10% glycerol, frozen with liquid nitrogen, and stored at -80 °C in aliquots.